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First-Trimester Inflammatory Markers for Risk Evaluation of Pregnancy Hypertension

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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.

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Acknowledgements

The work was funded by Indian Council of Medical Research (Grant Number 5/7/509/10-RHN).

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Authors and Affiliations

  1. Biochemistry, Lady Hardinge Medical College, New Delhi, India

    Karuna Sharma, Ritu Singh & Jayashree Bhattacharjee

  2. Obstetrics and Gynecology, Lady Hardinge Medical College, New Delhi, India

    Manisha Kumar

  3. ESIC Medical College, Faridabad, Haryana, India

    Usha Gupta

  4. Clinical Biochemistry, Vallabhbhai Patel Chest Institute, New Delhi, India

    Vishwajeet Rohil

Authors
  1. Karuna Sharma
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  2. Ritu Singh
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  3. Manisha Kumar
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  4. Usha Gupta
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Corresponding author

Correspondence to Karuna Sharma.

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Ethical statement

All procedures performed were with the standard of institutional research ethical committee and the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individuals who participated in the study.

Additional information

Karuna Sharma is a Ph. D. student in Biochemistry department of Lady Hardinge Medical College, New Delhi, India. Ritu Singh is in Biochemistry, Lady Hardinge Medical College, New Delhi, India. Manisha Kumar is in Obstetrics and Gynecology, Lady Hardinge Medical College, New Delhi, India. Usha Gupta is in ESIC Medical College, Faridabad, Haryana, India. Vishwajeet Rohil is in Clinical Biochemistry, Vallabhbhai Patel Chest Institute, New Delhi, India. Jayashree Bhattacharjee is in Biochemistry, Lady Hardinge Medical College, New Delhi, India.

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Sharma, K., Singh, R., Kumar, M. et al. First-Trimester Inflammatory Markers for Risk Evaluation of Pregnancy Hypertension. J Obstet Gynecol India 68, 27–32 (2018). https://doi.org/10.1007/s13224-017-0988-1

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  • DOI: https://doi.org/10.1007/s13224-017-0988-1

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