Introduction
Preeclampsia is known as the hypertensive disorder of pregnancy (HDP). It affects around two to eight percent of all pregnancies and is the main reason for maternal and perinatal morbidity and mortality. Preeclampsia is a complex disorder at the maternal-fetal interface involving multiple organ systems. Hypertension is the main reason behind the syndrome and is frequently, but not always, accompanied by proteinuria. The pathophysiology of preeclampsia is a complex process whose primary cause is abnormal placentation.
What Is Preeclampsia?
Preeclampsia is a critical blood pressure condition that occurs during pregnancy. People with preeclampsia frequently have high blood pressure (hypertension) and high protein levels in the urine (proteinuria). Preeclampsia usually occurs after the 20th week of pregnancy. It can also affect a few other organs in the body and be hazardous for the mother and the developing fetus. Because of these risks, preeclampsia needs to be treated timely by the doctors.
What Is Preeclampsia Pathophysiology?
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The pathophysiology of preeclampsia is a complex procedure. It involves acquired, genetic, and immune risk factors responsible for placental dysfunction. Placental dysfunction results in the release of anti-angiogenic factors that result in multiorgan dysfunction later.
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In addition to endothelial dysfunction, immunologic aberrations are also the factors that add to the preeclampsia phenotype. In normal pregnancy, T helper cells move toward the anti-inflammatory Th2 phenotype, which assists in neutralizing proinflammatory cytokines, angiotensin II type 1 receptor (AT1R) autoantibodies, placental reactive oxygen species, and endothelin-1. But, in preeclampsia, T helper cells move toward the Th1 phenotype, increasing the release of proinflammatory cytokines such as interleukin (IL)-12 and IL-18 and decreasing IL-10, which causes apoptosis and reduces the invasion of trophoblast. Increased CD19+CD5+ B lymphocytes might add to the production of antiangiogenic factors. Uterine natural killer cells, which are different from peripheral natural killer cells, are probably involved, as inhibition of uterine natural killer cells might cause defective spiral artery remodeling. Syncytial knots, vesicles shed from the trophoblasts, might stimulate an inflammatory response in the placenta. LIN28 is an RNA-binding protein that affects the metabolism of the cells, differentiation, development, and invasion. Two paralogs, LIN28A, and LIN28B, are present. LIN28B is elevated in extravillous trophoblasts or placenta in normal pregnancy. In preeclampsia, levels are reduced in the placenta. This indicates a role in preeclampsia by reducing trophoblast differentiation and invasion and promoting inflammation. Elevated levels of complement in preeclampsia result in the complement system, dysregulation, and additional increases in sFlt-1. Women suffering from preeclampsia have reduced histocompatibility complex human leukocyte antigen-G and -E, indicative of immune imbalance.
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Several genetic components have been implied in the pathogenesis of preeclampsia. Mutations in complement component 3 are associated with preeclampsia, which might partly account for complement system dysregulation. Corin, a cardiac protein that activates atrial natriuretic peptide, has also been localized to uterine tissue, and mutations in corin associated with preeclampsia have been noted. Global transcriptional profiling of chorionic villus samples of women with preeclampsia has a genetic susceptibility to preeclampsia. Endometrial stromal cells from nonpregnant women with a history of severe preeclampsia failed to decidualize in vitro. They were transcriptionally inert, and decidual tissue from women with preeclampsia revealed defects in gene expression.
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Long-chain L-3 hydroxy acyl-CoA dehydrogenase deficiency (a disorder of fatty acid metabolism) has been associated with preeclampsia. A study revealed that women who develop preeclampsia are more prone to carry loss-of-function mutations in 43 genes associated with idiopathic dilated and peripartum cardiomyopathy. The TTN gene, which encodes the sarcomeric protein titin, possesses the highest frequency of mutations. Genome-wide association studies have shown both single nucleotide polymorphism rs4769613, near the FMS-like tyrosine kinase 1 gene, and Rs9478812, within protein PLEKHGI, which is implicated in the regulation of blood pressure (BP), to be associated with preeclampsia. No other mutations of placental growth factor, sFlt-1, or sEng genes have been identified till now. However, next-generation sequencing, or massively parallel sequencing, allows affordable evaluation of large genomic regions and is an efficient tool for studying the genetic influence on preeclampsia.
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Lastly, a few inherited risk factors have been shown to elevate the risk of preeclampsia. Obesity (body mass index >30) and diabetes each carry a relative risk increase of preeclampsia. Chronic hypertension, chronic kidney disease, obstructive sleep apnea, pre-gestational diabetes, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, maternal age over 35 years, nulliparity, multifetal gestations, fetal hydrops, hydatidiform moles, and assisted reproductive technologies are also seen to have preeclampsia. Though abnormal placentation might cause the early development of preeclampsia, the preceding information suggests an underlying role of pre-existing cardiovascular and other organ dysfunction before conception.
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Preeclampsia is also associated with long-term consequences following delivery, particularly cardiovascular issues. Studies reveal that preeclampsia's prior causes are associated with higher rates of hypertension, ischemic heart disease or recurrent acute coronary syndrome, heart failure, stroke, and death. Further study into the cardiovascular structure and function deformities might show potential areas for clinical intervention to slow disease risk and burden.
How Is Preeclampsia Treated?
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Treatment for preeclampsia frequently depends on how severe the preeclampsia is and how long a woman is pregnant. If the pregnancy is close to full term (37 weeks pregnant or greater), the baby will be delivered early probably. A woman can still have a vaginal delivery, but sometimes a cesarean delivery (C-section) might be advised. The doctors might give medication to help the fetus's lung development and blood pressure management until the baby is delivered. Sometimes it is safe to deliver the baby early than to risk the pregnancy by prolonging it.
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In the cases where preeclampsia is developed at an earlier stage in the pregnancy, proper monitoring of the woman is done to prolong the pregnancy and allow proper growth and development of the fetus. It is advised to check blood pressure at home also.
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During labor and after the delivery, women with preeclampsia are often administered magnesium intravenously (directly into the vein) to prevent the development of eclampsia (seizures from preeclampsia).
Conclusion
Preeclampsia is a condition in which the blood pressure of the females becomes elevated during pregnancy. Its pathophysiology depends on various factors such as genetics, age, conditions like diabetes, cardiac issues, etc.
