High-risk individuals and the Etiological Factors of Preeclampsia

What is Preeclampsia?

Preeclampsia is a multi-organ syndrome that develops in the latter half of pregnancy, classically defined by the presence of hypertension accompanied by proteinuria or multi-organ dysfunction.

-  Hypertension in pregnancy is defined as the elevation of blood pressure after 20 weeks of gestation, measured on at least two occasions spaced at least 4 hours apart. In cases of pre-existing chronic hypertension where the following additional factors emerge, the condition is classified as superimposed preeclampsia on chronic hypertension.

- The key signs and symptoms used to diagnose preeclampsia include:

• Proteinuria: ≥300 mg protein on 24-hour urine collection, or Protein/creatinine ratio ≥30 mg/mmol
• Renal impairment: Serum creatinine ≥90 μmol/L
• Hepatic dysfunction: Liver enzyme levels elevated 2x above the normal range, or having abnormal upper quadrant pains
• Neurological complications: Eclampsia, stroke, altered mental status, severe headaches, visual disturbances, temporary blindness
• Hematological complications: Thrombocytopenia (<150,000/dL), Disseminated intravascular coagulation, or Hemorrhage

Who is having a high risk of preeclampsia?  

According to the recommendations of the American College of Obstetricians and Gynecologists (ACOG), the following groups are identified as high-risk populations and should receive preventive treatment:

• Primigravida
• Multifetal pregnancy (twins, triplets, etc.)
• Having a history of preeclampsia in the previous pregnancy
• Systemic lupus erythematosus (SLE)
• Hemophilia
• Chronic hypertension - Hemophilia
• Pre-pregnancy body mass index (BMI) over 35 kg/m2
• Antiphospholipid syndrome
• Diabetes mellitus or gestational diabetes
• Maternal age over 35 years
• Renal disorders
• Obstructive sleep apnea
• Using assisted reproductive technologies

However, if we only follow the recommendations of ACOG, doing so could result in failing to identify and treat up to 50% of the individuals who require medical intervention.

The biological mechanism of Preeclampsia

When the embryo implants into the uterus and creates the fetus and the placenta, the trophoblast cells of the placenta then invade the spiral arteries of the mother’s uterus, and new blood vessels form to ensure a sufficient blood supply to the placenta.

In the case of women with preeclampsia, the development of these vascular structures appears to be inadequate. The placenta releases various substances into the maternal spiral arteries, including two distinct factors:

• PIGF: A pro-angiogenic factor that promotes vascular growth, facilitating improved placental development and enhanced nutrient delivery from the mother to the fetus.
• sFlt1: An anti-angiogenic factor that helps to prevent the vascular system from becoming excessive and overtaking the maternal organism, ensuring fetal development does not compromise the mother's well-being.

The ratio between the sFlt1 and PIGF factors fluctuates throughout the course of gestation. When this ratio is balanced, it helps the fetus develop without adversely impacting maternal health (this balance is not a 1:1 ratio, but rather varies across different populations and ethnicities).

When the placenta experiences inadequate perfusion, the trophoblast cells fail to adequately invade the maternal spiral arteries for some reason, leading to an imbalance between the two key factors, sFlt1 and PIGF, which in turn results in the development of preeclampsia, with the maternal blood pressure become elevated.

An sFlt1/PlGF ratio > 38 is associated with an adverse pregnancy prognosis, irrespective of whether the patient develops clinical preeclampsia. Pregnant women presenting with an elevated sFlt1/PIGF ratio above this threshold have a 2.9-fold increased risk of preterm delivery.

The preterm birth rate is up to 71% higher in pregnant women with an sFlt-1/PlGF ratio exceeding 38, compared to those with a ratio below 38. For those with an elevated sFlt1/PIGF ratio above 38, the median time to delivery is approximately 17 days (causing preterm birth or the development of complications from preeclampsia that require abortion). In contrast, those with an sFlt1/PIGF ratio below 38 have a median time to delivery of 51 days.

Preeclampsia Testing at GENTIS

First Trimester: PlGF index (gestational weeks 11-14) combined with maternal history, clinical examination findings, and ultrasound results.

Second and Third Trimesters: sFLT-1/PIGF ratio to predict adverse pregnancy outcomes in pregnant women.

• Second Trimester: 19 weeks 1 day to 24 weeks 6 days
• Third Trimester: 30 weeks to 37 weeks 6 days
• Sample required: 2 ml peripheral blood
• Turnaround time: 2 days

Preeclampsia is a severe obstetric event that requires close monitoring, as it can lead to numerous hazardous complications for both the mother and the baby. The prevention of complications can occur early if you adhere to comprehensive prenatal care and follow the pregnancy monitoring advice provided by the physician.