There are 2 clusters of term preeclampsia, supporting evidence of the disease’s heterogeneity, according to a recent study published in the American Journal of Obstetrics & Gynecology.
Takeaways
- Preeclampsia, affecting 3% to 7% of pregnancies, remains a significant cause of maternal and perinatal morbidity and mortality, with its prevalence rising in the United States, potentially linked to increasing obesity rates.
- The heterogeneity of preeclampsia is highlighted by the recommendation to categorize it based on onset and pathophysiological factors, such as "early- or late-onset" and "placental or maternal preeclampsia."
- Intravascular inflammation plays a crucial role in preeclampsia's pathogenesis, alongside the antiangiogenic state, yet understanding how these factors interact remains a challenge.
- A nested case-control study revealed distinct profiles among women with preeclampsia at term, with variations in angiogenic profiles, cytokine concentrations, and adverse maternal outcomes.
- Accurate subclassification of preeclampsia patients is essential for both research and clinical practice, offering insights into tailored management approaches and improved outcomes.
Preeclampsia has been reported in 3% to 7% of pregnancies, making it one of the leading causes of maternal and perinatal morbidity and mortality. A significant increase in disease onset has been observed in the United States in the previous 10 years, linked to rising obesity rates.
Data has indicated heterogeneity of preeclampsia, with experts recommending categorizing the disease as “early- or late-onset” and “placental or maternal preeclampsia.” However, challenges have persisted for prediction and prevention of preeclampsia at term.
Preeclampsia pathophysiology may be influenced by intravascular inflammation, but there is little data about how exaggerated intravascular inflammation coexists with an antiangiogenic state, which is central to the disease’s pathogenesis. To further evaluate the pathophysiology of preeclampsia at term, investigators conducted a nested case–control study.
Participants included women with preeclampsia at term and an available blood sample collected within 1 week before delivery. Study cohorts included women with preeclampsia at term and a normal angiogenic profile, those with preeclampsia and an abnormal angiogenic profile, and those with an uncomplicated pregnancy.
Exclusion criteria included multiple gestation, major obstetric complication, severe medical illness, chronic hypertension, asthma requiring steroids, active hepatitis, fetal anomalies, and needing antiplatelet or nonsteroidal anti-inflammatory drugs.
Preeclampsia was determined by hypertension onset after 20 weeks’ gestation and proteinuria, with hypertension defined as systolic 140 mm Hg or higher or diastolic 90 mm Hg or higher blood pressure. Blood pressure was measured twice, with a duration between 4 hours and 1 week separating measurements.
A urine protein level over 300 mg indicated proteinuria. Composite adverse maternal outcomes included stroke, blindness, eclampsia, elevated liver enzymes, myocardial ischemia, pulmonary edema, thrombocytopenia, acute kidney injury, hepatic hematoma, disseminated intravascular coagulopathy, placental abruption, and maternal death.
Histological evaluation of placentas was also performed, with Perinatology Section of the Society for Pediatric Pathology and Amsterdam Placental Workshop Group criteria used to diagnose placental lesions consistent with maternal vascular malperfusion.
Higher rates of nulliparity and an increased body mass index (BMI) were observed in patients with preeclampsia vs those without preeclampsia. Obesity was more common in those with preeclampsia at term and a normal angiogenic profile.
Increased median systolic and diastolic blood pressure volumes were observed among women with an abnormal angiogenic profile. These patients also had increased rates of severe hypertension, small for gestational age newborns, and placental lesions of maternal vascular malperfusion, at 56%, 39%, and 48%, respectively.
Median plasma concentrations of 5 cytokines were also increased among patients with preeclampsia and an abnormal angiogenic profile, those being interleukin (IL)-6, IL-8, IL-12, IL-15, and IL-16. Seven chemokines also had higher median plasma concentrations among these patients vs those with an uncomplicated pregnancy.
Compared to women with a normal angiogenic profile, those with an abnormal angiogenic profile had higher median plasma concentrations for 2 cytokines and 3 chemokines. Additionally, the median concentration of growth factors granulocyte-macrophage colony-stimulating factor was lower in these patients.
When comparing women with preeclampsia at term to women with an uncomplicated pregnancy, only MCP-4 had a significantly increased median plasma concentration following adjustments for BMI and nulliparity. An association was also found between systolic blood pressure and diastolic blood pressure values with plasma IL-6 concentrations.
These results indicated increased intravascular inflammation among women with preeclampsia at term vs those with an uncomplicated pregnancy. Investigators concluded, “accurate subclassification of patients with preeclampsia is important in both experimental and clinical research.”
Reference
Chaiworapongsa T, Romero R, Gomez-Lopez N, et al. Preeclampsia at term: evidence of disease heterogeneity based on the profile of circulating cytokines and angiogenic factors. Am J Obstet Gynecol. 2024;230:450.e1-18. doi:10.1016/j.ajog.2023.10.002
