Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis.
OBJECTIVE
To review maternal and foetal outcomes in women with mechanical heart valves (MHVs) treated with vitamin-K antagonists (VKAs), first-trimester heparin followed by VKAs (sequential treatment), low molecular weight heparin (LMWH) and unfractionated heparin (UFH) during pregnancy, in order to inform practice.


RESULTS
Medline, Embase and Central were searched from inception until February 2016. Two reviewers independently screened 1786 titles, reviewed 110 full-texts and extracted data and assessed risk-of-bias from 46 articles. Pooled incidence (95% confidence intervals) was calculated for maternal and foetal outcomes. Included studies had a moderate or high risk-of-bias. With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4-1.4), 2.0% (0.8-3.1) and 2.9% (0.2-5.7), thromboembolic complications in 2.7% (1.4-4.0), 5.8% (3.8-7.7) and 8.7% (3.9-13.4), livebirths in 64.5% (48.8-80.2), 79.9% (74.3-85.6) and 92.0% (86.1-98.0) and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3-3.7), 1.4% (0.3-2.5) and 0%, respectively. When UFH is used throughout pregnancy, 11.2% (2.8-19.6) suffered thromboembolic complications. Foetal loss and adverse events occurred with first-trimester warfarin doses ≤ 5 mg/day, although there were more livebirths [83.6% (75.8-91.4) vs. 43.9% (32.8-55.0)] and fewer foetal anomalies [2.3% (0.7-4.0) vs. 12.4% (3.3-21.6)] with lower doses than with warfarin > 5 mg/day.


CONCLUSIONS
VKAs are associated with fewest maternal complications but also with fewest livebirths. Sequential treatment does not eliminate anticoagulant-related foetal/neonatal adverse events. LMWH is associated with the highest number of livebirths. The safety of UFH throughout pregnancy and first-trimester warfarin  ≤ 5 mg/day remains unconfirmed.
Department of Obstetrics and Gynaecology, Division of Maternal and Fetal Medicine, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto ON M5T 3M6, Canada.
Rohan
R
D'Souza
Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada.
Jackie
J
Ostro
Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto ON M5T 3M6, Canada.|Department of Paediatrics, Division of Neonatology, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Prakesh S
PS
Shah
Department of Medicine, Division of Cardiology, Obstetric Medicine Program, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Candice K
CK
Silversides
Department of Obstetrics and Gynaecology, Division of Maternal and Fetal Medicine, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Ann
A
Malinowski
Department of Obstetrics and Gynaecology, Division of Maternal and Fetal Medicine, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto ON M5T 3M6, Canada.
Kellie E
KE
Murphy
Department of Obstetrics and Gynaecology, Division of Maternal and Fetal Medicine, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Mathew
M
Sermer
Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto ON M5T 3M6, Canada.|Departments of Medicine and Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Division of Hematology, Mount Sinai Hospital, University of Toronto, 700 University Avenue, Toronto ON M5G 1Z5, Canada.
Nadine
N
Shehata
D000925:Anticoagulants / Q000009:adverse effects*; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005315:Fetal Diseases / Q000139:chemically induced; D006350:Heart Valve Prosthesis; D006493:Heparin / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008428:Maternal Mortality; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000628:therapy*; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D013923:Thromboembolism / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000009:adverse effects
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D014859:Warfarin; D006493:Heparin
Anticoagulation ; Heparin; Mechanical heart valves ; Pregnancy ; Vitamin-K antagonists 