What is Preeclampsia?
Preeclampsia is a complication during pregnancy associated with high blood pressure (greater than 140/90 mmHg). Possible associated complications can include damage to the liver and kidneys, fluid retention, and swelling. Preeclampsia may be related to problems with the placenta and thus, may impair fetal growth and lead to preterm birth or even a stillbirth (if the placental abruption leads to heavy bleeding in the mother). Offsprings of mothers who had preeclampsia are at a higher risk for long-term health issues such as learning disorders, epilepsy, blindness, and cerebral palsy.
The Biochemistry of Preeclampsia
While the exact cause of preeclampsia has yet to be determined, a study found significant alterations in the metabolites in the first-trimester serum of women destined to develop late preeclampsia. Particularly, there were anomalies in the branch chain amino acids (valine, leucine, and isoleucine), glycolysis, gluconeogenesis, and ketone body metabolic pathways. A study found increased levels of glucose and glycerol with perturbations of lipid metabolism. These observed changes indicate abnormal lipid metabolism, which is implicated in the pathogenesis of late preeclampsia. Moreover, valine, leucine, and isoleucine were found to be significantly upregulated in first-trimester serum samples. These amino acids play a large role in carbohydrate synthesis and fat synthesis and are implicated in predicting future insulin resistance that can be observed in the development of PE. In general, the observed differences (increased glucose and levels of certain amino acids) indicates that an increased BMI might be related to the development and progression of preeclampsia. Furthermore, this study indicates that analysis of the first-trimester serum of those with late-onset preeclampsia shows an increased pyruvic acid concentration and lactate. This suggests a disturbance in glycolysis and gluconeogenesis because hypoxia and oxidative stress are features of preeclampsia.
Sociodemographic Risks
Apart from genetic influences, another major risk for the development of preeclampsia involves social factors. Women with a lower socioeconomic background may be associated with poor prenatal care and nutritional deficits, which can increase the risk of disturbances in glycolysis and gluconeogenesis and by proxy, preeclampsia.
Bahado-Singh, Ray O., et al. “Metabolomic Determination of Pathogenesis of Late-Onset Preeclampsia.” The Journal of Maternal-Fetal & Neonatal Medicine, vol. 30, no. 6, 2016, pp. 658–664., doi:10.1080/14767058.2016.1185411.K, R., Gandhi, S., & Rao, V. (2014). Socio-Demographic and Other Risk Factors of Pre Eclampsia at a Tertiary Care Hospital, Karnataka: Case-Control Study. Journal of Clinical and Diagnostic Research : JCDR, 8(9), JC01–JC04. http://doi.org/10.7860/JCDR/2014/10255.4802
What I found interesting from this article was the BCAA's the researchers found that were up regulated during the first trimester. After reading this, I wondered what type of future treatment intervention can be created because of this, for example I wonder if siRNA's can be used in women with the risk factors for preeclampsia to knock down gene regulation, can essentially normalize their gene expression. Moreover, I also found interesting was the several pathways that contribute to the disturbances in glycolysis and gluconeogenesis including BCAA's, increased pyruvic acid and lactate concentrations, and a genetic component. I wonder if one of these pathways plays a larger role in the development of preeclampsia compared to the others?
ReplyDeleteThis is a really interesting post! I feel as if I learned some very useful information here. Most of what I know of preeclampsia up until now is that some signs to look for in mothers are hypertension and high protein levels in urine. The proteinuria is related to issues that arise with the kidneys, as you mention. Preeclampsia is daunting because, although there are definitely sociodemographic factors that may predispose women to developing the condition, we just don't know enough about it or what to do with it past a certain point and it therefore is one of the most common causes of maternal mortality even in developed countries such as the U.S.
ReplyDeleteI would like to make the distinction, though, that what you are indeed talking about with this study is specifically regarding late-onset preeclampsia, which is considered to be when onset is at 34 weeks gestation or after. From what I'm reading, it seems their pathologies do differ quite a bit, and early-onset is generally the one with placental pathology. In my search I have not found anything, but in your research regarding this topic did you find any information to link these BCAA anomalies to early-onset preeclampsia as well?
For anyone reading who may be interested, here is a link to a 2017 article comparing/contrasting early-onset and late-onset preeclampsia: https://www.sciencedirect.com/science/article/pii/S2210778916303592