First-Trimester Inflammatory Markers for Risk Evaluation of Pregnancy Hypertension.

Introduction: Hypertension in pregnancy is one of the potential causes of maternal and fetal morbidity and mortality. It complicates 7-10% of pregnancies. As of today, prediction of pregnancy hypertension is not possible.

Aim and Objectives: Evaluation of pregnancy associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin, tumor necrosis factor-α (TNF-α) and interferon gamma (INF-γ) in establishing a biomarker or combination of biomarkers for the early identification of pregnancy hypertension.

Methodology: This prospective study was carried out in two phases. Phase I was a cohort study in which 2000 pregnant women were enrolled in their first trimester (11 + 0 to 13 + 6 weeks of gestation) and followed till delivery. Women who developed hypertension were compared with normotensive cohort (women who remained normotensive till term). Phase II was a case-control study. The women who were diagnosed with hypertension in phase I were cases and their controls were matched for gestational age and sample storage time from normotensive cohort population. Two additional proinflammatory markers TNF-α and INF-γ were evaluated in this case-control population.

Results: Out of 2000 women, 199 women developed hypertension and 1454 women remained normotensive throughout their pregnancy. Among 199 hypertensive women, 151 (9.13%) cases had gestational hypertension, 45 (2.72%) had preeclampsia (PE) and 3 (0.18%) had eclampsia (E). First trimester mean arterial pressure (MAP) ( p  < 0.001) and body mass index (BMI) ( p  < 0.001) were found significantly higher in hypertensive women when compared with normotensive women. Maternal serum levels of PAPP-A ( p  < 0.001) were significantly low in hypertensive women as compared to normotensive women, while free β-hCG ( p  = 0.59) was high, but the difference was not statistically significant. TNF-α ( p   <  0.001) and INF-γ ( p  = 0.014) both were high in hypertensive women. When all biomarkers were combined we found the positive predictive value (PPV) of 51.6% an negative predictive value (NPV) of 71.4%.

Conclusion: Increased levels of proinflammatory cytokines suggest the role of underlying inflammation in pathogenesis of pregnancy hypertension, and low PAPP-A may be attributed to impaired implantation. Combining biomarkers may improve the prediction of pregnancy hypertension in the early stages of gestation. NPV of 71.4% depicts that if woman has all biomarkers in normal ranges during first trimester, she will have 71.4% chances of remaining normotensive during pregnancy.