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. 2018 Feb;68(1):27-32.
doi: 10.1007/s13224-017-0988-1. Epub 2017 Apr 19.

First-Trimester Inflammatory Markers for Risk Evaluation of Pregnancy Hypertension

Karuna Sharma  1 , Ritu Singh  1 , Manisha Kumar  2 , Usha Gupta  3 , Vishwajeet Rohil  4 , Jayashree Bhattacharjee  1
Affiliations

First-Trimester Inflammatory Markers for Risk Evaluation of Pregnancy Hypertension

Karuna Sharma et al. J Obstet Gynaecol India. 2018 Feb.

Abstract

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.

Keywords: Free β-hCG; INF-γ; PAPP-A; Pregnancy hypertension; TNF-α.

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Conflict of interest statement

Compliance with Ethical StandardsNone.All procedures performed were with the standard of institutional research ethical committee and the 1964 Helsinki declaration and its later amendments.Informed consent was obtained from all individuals who participated in the study.

Figures

Fig. 1
Fig. 1
Flow chart showing total population stratification
See this image and copyright information in PMC

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