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Angiogenic factors during pregnancy in Asian women with elevated blood pressure in early pregnancy and the risk of preeclampsia: a longitudinal cohort study
  1. Jing Zhu1,
  2. Jun Zhang1,2,
  3. Mor Jack Ng2,
  4. Bernard Chern2,
  5. George SH Yeo3,
  6. Kok Hian Tan2
  1. 1 MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  2. 2 Division of Obstetrics and Gynaecology, KK Women's and Children's Hospital, Singapore, Singapore
  3. 3 Department of Maternal and Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore
  1. Correspondence to Dr Jun Zhang; junjimzhang{at}sina.com

Abstract

Objective It remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia.

Design A prospective cohort study.

Setting KK Women’s and Children’s Hospital, Singapore.

Participants 923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11–14 weeks.

Primary and secondary outcomes Maternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11–14, 18–22, 28–32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome.

Results Women were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11–14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively.

Conclusion Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal.

  • blood pressure
  • soluble fms-like tyrosine kinase 1
  • placental growth factor
  • preeclampsia

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors JZ: performed the statistical analysis, searched literature and drafted the manuscript. JZ (corresponding author): had the original idea, provided guidance for the statistical analysis and revised the manuscript. MJN, BC, GSHY and KHT: participated in the data collection, reviewed and revised the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the SingHealth Centralised Institutional Review Board Ethics Committee, Singapore (CIRB Ref No. 2010/214/D).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.