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Review
. 2017 Jun 6;69(22):2681-2691.
doi: 10.1016/j.jacc.2017.03.605.

Maternal and Fetal Outcomes of Anticoagulation in Pregnant Women With Mechanical Heart Valves

Zachary L Steinberg  1 , Clara P Dominguez-Islas  2 , Catherine M Otto  3 , Karen K Stout  3 , Eric V Krieger  3
Affiliations
Review

Maternal and Fetal Outcomes of Anticoagulation in Pregnant Women With Mechanical Heart Valves

Zachary L Steinberg et al. J Am Coll Cardiol. .

Abstract

Background: Anticoagulation for mechanical heart valves during pregnancy is essential to prevent thromboembolic events. Each regimen has drawbacks with regard to maternal or fetal risk.

Objectives: This meta-analysis sought to estimate and compare the risk of adverse maternal and fetal outcomes in pregnant women with mechanical heart valves who received different methods of anticoagulation.

Methods: Studies were identified using a Medline search including all publications up to June 5, 2016. Study inclusion required reporting of maternal death, thromboembolism, and valve failure, and/or fetal spontaneous abortion, death, and congenital defects in pregnant women treated with any of the following: 1) a vitamin K antagonist (VKA) throughout pregnancy; 2) low-molecular-weight heparin (LMWH) throughout pregnancy; 3) LMWH for the first trimester, followed by a VKA (LMWH and VKA); or 4) unfractionated heparin for the first trimester, followed by a VKA (UFH and VKA).

Results: A total of 800 pregnancies from 18 publications were included. Composite maternal risk was lowest with VKA (5%), compared with LMWH (16%; ratio of averaged risk [RAR]: 3.2; 95% confidence interval [CI]: 1.5 to 7.5), LMWH and VKA (16%; RAR: 3.1; 95% CI: 1.2 to 7.5), or UFH and VKA (16%; RAR: 3.1; 95% CI: 1.5 to 7.1). Composite fetal risk was lowest with LMWH (13%; RAR: 0.3; 95% CI: 0.1 to 0.8), compared with VKA (39%), LMWH and VKA (23%), or UFH and VKA (34%). No significant difference in fetal risk was observed between women taking ≤5 mg daily warfarin and those with an LMWH regimen (RAR: 0.9; 95% CI: 0.3 to 2.4).

Conclusions: VKA treatment was associated with the lowest risk of adverse maternal outcomes, whereas the use of LMWH throughout pregnancy was associated with the lowest risk of adverse fetal outcomes. Fetal risk was similar between women taking ≤5 mg warfarin daily and women treated with LMWH.

Keywords: fetal risk; maternal risk; pregnancy.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Study Search Flowchart The number and types of studies captured by the search terms. INR = international normalized ratio; LMWH = low-molecular-weight heparin; PVR = pulmonary valve replacement; TVR = tricuspid valve replacement; UFH = unfractionated heparin.
Figure 2
Figure 2
Forest Plot of the Composite Maternal Outcome The individual and composite maternal endpoints as reported by each publication included in the meta-analysis. The forest plot represents an averaged risk of the composite outcome, weighted by study sample size. *Values in brackets are number of deaths, number of prosthetic valve failures or thromboembolisms. CI = confidence interval; VKA = vitamin K antagonist; other abbreviations as in Figure 1.
Figure 3
Figure 3
Forest Plot of the Composite Fetal Outcome The individual and composite fetal endpoints as reported by each publication included in the meta-analysis. The forest plot represents an averaged risk of the composite outcome, weighted by study sample size. *Values in brackets are number of spontaneous abortions, number of fetal deaths, number of births with congenital defects. Abbreviations as in Figures 1 and 2.
Figure 4
Figure 4
Maternal Composite Outcome Ratio of the meta-analytic averaged risk for the maternal composite outcome between a VKA regimen and each alternative regimen. Abbreviations as in Figures 1 and 2.
Figure 5
Figure 5
Fetal Composite Outcome (A) Ratios of the meta-analytic averaged risk for the fetal composite outcome between a VKA regimen and each alternative regimen. (B) Ratio of averaged risk for the fetal composite outcome between a low-dose VKA regimen and the alternative regimens. Abbreviations as in Figures 1 and 2.
Central Illustration
Central Illustration
Anticoagulation Strategies in Pregnant Women With Mechanical Heart Valves This illustration depicts maternal and fetal risk with different anticoagulation regimens. Maternal risk is lowest on a vitamin K antagonist (VKA) regimen, and fetal risk is lowest on a low-molecular-weight heparin (LMWH) regimen. The risk of either a maternal or fetal complication during pregnancy is lowest with a low-dose warfarin regimen; however, even low-dose warfarin carries a substantial risk of a poor outcome. CI = confidence interval.
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