Its All About: Preeclampsia

Childbirth, while perhaps one of the most intricate and beautiful natural physiological processes, can present its own challenges ranging from milder issues like morning sickness to more nefarious complications such as preeclampsia. Classified as a hypertensive disorder of pregnancy, preeclampsia presents a rather idiosyncratic set of challenges as its pathological consequences are not limited to just the mother or just the fetus pitting one against the other. What was meant to be a natural demonstration of symbiosis, often turns into a battle for survival lending itself as one of the most dangerous complications in pregnancy affecting between 5%-7% of women worldwide with roughly 70,000 to 500,000 fetal deaths worldwide. It is also the leading cause of maternal mortality, C-sections, and maternal morbidity in the United States. Preeclampsia can be defined as new-onset hypertension with new-onset proteinuria that develops after 20 weeks of gestation in previously normotensive patients (Rana et al., 2019). Severe complications arise due to systemic manifestations of preeclampsia which include thrombocytopenia, elevated LFTs, and pulmonary edema. Unfortunately, a significant amount of women may develop these more severe features before a diagnosis is made. Furthermore, the true mechanism of its pathogenesis is yet to be elucidated. Research stipulates that the problem may reside in the placenta in the form of uteroplacental ischemia resulting in acute hypertensive syndrome (Portelli et al., 2018).

Symptomatic presentation of preeclampsia is not at all concrete and may be considered fulminant or of gradual progression ranging in severity. In fact, some women, while clinically presenting with hypertension and proteinuria, may be asymptomatic while others may present with severe systemic complications at onset. As mentioned above, symptomatic presentation is multi-etiological. In a general sense, the initial signs of preeclampsia are hypertension and proteinuria resulting in water retention, but photosensitivity and dark spots in the vision may also present. Symptoms of high blood pressure include dizziness, shortness of breath, headaches, fatigue, and more. Whereas proteinuria may lead to oliguria - increased frequency of urination, swelling in the face and hands due to edema, and possibly nocturnal muscle cramps. Severe systemic manifestations can lead to symptoms such hypertensive emergency (BP > 160/110 mmHg), reduced liver and kidney function, pulmonary edema, and thrombocytopenia (low platelet count). In rare cases, preeclampsia can progress into eclampsia which can present with neurological symptoms including brain edema, epileptic seizures, and cerebral hemorrhaging (Portelli et al., 2018). Recognition of any of these symptoms at roughly 20 weeks gestational age is key for optimal therapeutic management and safety for both the mother and fetus.

As with many pathologies, preeclampsia is associated with solidified risk factors, and knowing them can make a difference in arriving at a diagnosis for the patient as well as help increase a patient’s awareness. Major risk factors include, firstly, any previous history of preeclampsia, diabetes mellitus, obesity, antiphospholipid syndrome, and chronic hypertension. However, advanced maternal age, nulliparity (unable to carry a child to term), chronic kidney disease, and use of assisted reproductive technologies may also contribute to the onset of preeclampsia. Genetic errors and susceptibility, although novel, have also proven to be useful in identification of those who are more predisposed to developing preeclampsia. A genome associated study of 4,380 neonates born from mothers affected with preeclampsia revealed susceptibility in the FLT1 (FMS-like tyrosine kinase 1) gene which is now a well established genetic factor in preeclampsia (Rana et al., 2019). While some of the risk factors are intrinsic in nature and dependent on history, there are factors which can be somewhat controlled and managed to aid in prevention of preeclampsia.

Diagnosis of preeclampsia often occurs during routine prenatal appointments. Healthcare providers’ assessment of blood pressure and urine has high diagnostic relevance. The ACOG committee 2017 guidelines stipulates that recommended screening to predict preeclampsia should not go beyond obtaining baseline values and medical histories. However, the Fetal Medicine Foundation believes that an algorithmic screening method which takes into account maternal factors, mean arterial pressure, PIGF (placental growth factor), and uterine-artery pulsatility may prove to be more specific in identifying patients with preeclampsia over the ACOG and NIH’s recommendation (Rana et al., 2019). Regardless, identification of the initial symptoms and severe manifestation are necessary. In addition to blood pressure and urinalysis, ordering of liver function tests and platelet count if indicated should be observed. Currently, in the age of molecular medicine, biomarkers have been investigated for preeclampsia screening. While novel, the reliability of these markers is not yet solidified as they have been inconsistent in their sensitivity in different studies. Some of the major proposed biomarkers include sFlt-1 (soluble fms-like tyrosine kinase 1), PIGF (placental growth factor), ADMA (Asymmetric Dimethyl-Arginine), and sEng (Soluble Endoglin) (Portelli et al., 2018). We have a bright future to look forward to as newer and more accurate screening tools are being developed.

Management of preeclampsia is dependent on the symptomatic presentation of the individual patient. However, in patients presenting with hypertension and proteinuria, perinatal BP control, prenatal aspirin therapy in high risk women, betamethasone for patients under 34 weeks gestational age, magnesium sulfate, and careful monitoring are indicated (Rana et al., 2019). The only definitive mainstay treatment is adequate delivery of the fetus and placenta. In patients with severe clinical manifestation, the appropriate management protocols are indicated depending on which symptoms are present. As a rule of thumb, patients with preeclampsia not presenting with severe problems should see their physician two times a week until 37 weeks gestational age. In addition the ACOG actually does not recommend pharmacological therapy for patients presenting with mild to moderate hypertension. Patients with severe hypertension should be put on labetalol and or amlodipine/nifedipine (Rana et al., 2019). Novel small molecular biological agents are currently being studied but have not yet received FDA approval.

References

Rana, S., Lemoine, E., Granger, J. P., & Karumanchi, S. A. (2019). Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circulation research, 124(7), 1094–1112. https://doi.org/10.1161/CIRCRESAHA.118.313276

Portelli M, Baron B. Clinical Presentation of Preeclampsia and the Diagnostic Value of Proteins and Their Methylation Products as Biomarkers in Pregnant Women with Preeclampsia and Their Newborns. J Pregnancy. 2018 Jun 28;2018:2632637. doi: 10.1155/2018/2632637. PMID: 30050697; PMCID: PMC6046127.