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Antithrombin improves the maternal and neonatal outcomes but not the angiogenic factors in extremely growth-restricted fetuses at <28 weeks of gestation

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Published/Copyright: December 3, 2016

Abstract

Aims:

Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤5th centile) at <28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared.

Results:

In group 1 (n=4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n=3) and 3 (n=7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes.

Conclusions:

The evaluation of the maternal sFlt-1 and PlGF at 21–27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health.


Correspondence author: Hiroshi Sameshima, MD, Department of Obstetrics and Gynecology and Center for Perinatal Medicine, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan, Tel.: +81-985-85-0988, Fax: +81-985-85-6149

Acknowledgements

We are grateful to Dr. Yuichiro Sato of the Department of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, for his assistance. This study was supported by a Grant (#79-258) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, a grant from the JAOG Ogyaa Donation Foundation (2014), and a research grant from CSL Behring, Tokyo, Japan.

Author’s statement

  1. Conflict of interest: The corresponding author (HS) received a research grant from CSL Behring, Tokyo, Japan (a total of 20,000 USD for research related to this study during 2013–2014). Except this, all authors declare no conflict of interest.

  2. Material and methods: Informed consent: Informed consent has been obtained from all individuals included in this study.

  3. Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

References

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Received: 2016-6-1
Accepted: 2016-10-12
Published Online: 2016-12-3
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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