Do women with a history of intrauterine fetal death require Low Molecular Weight Heparin (LMWH) in subsequent pregnancies?

LMWH for Women with History of Intrauterine Fetal Death in Subsequent Pregnancy

Women with a history of intrauterine fetal death (IUFD) alone do not routinely require LMWH in subsequent pregnancies unless they have additional risk factors such as prior VTE, documented thrombophilia, or antiphospholipid syndrome. The evidence does not support universal LMWH prophylaxis for isolated IUFD history.

Evidence-Based Recommendations by Clinical Scenario

When LMWH IS Indicated

For women with IUFD AND a history of VTE:

• Antepartum prophylaxis with LMWH is strongly recommended if the prior VTE was unprovoked or associated with hormonal risk factors 1
• Postpartum prophylaxis with LMWH for 6 weeks is strongly recommended for all women with prior VTE, regardless of the circumstances 1
• Women with prior pregnancy-associated VTE have a 4.5% recurrence risk in subsequent pregnancies, compared to 2.7% for unprovoked VTE 2

For women with IUFD AND documented thrombophilia:

• LMWH prophylaxis is suggested only for high-risk thrombophilias (antithrombin deficiency, homozygous factor V Leiden, or combined thrombophilias) 1
• Women heterozygous for factor V Leiden or prothrombin mutation, or those with protein C/S deficiency, should NOT receive routine antepartum prophylaxis regardless of family history 1

For women with IUFD AND antiphospholipid syndrome:

• LMWH combined with aspirin is the standard treatment for preventing recurrent pregnancy loss in women meeting laboratory criteria for antiphospholipid syndrome 1

When LMWH IS NOT Indicated

For women with isolated IUFD and no other risk factors:

• The highest quality randomized controlled trial (2015,449 patients) demonstrated that LMWH does not improve live-birth rates in women with unexplained recurrent pregnancy loss, showing 86.0% live births with LMWH versus 86.7% without (absolute difference -0.7%) 3
• A 2012 multicenter RCT (135 women) found no benefit of nadroparin in preventing recurrent late pregnancy complications including IUFD, with 21% events in the LMWH group versus 18% in controls 4
• A Cochrane review concluded that evidence is too limited to recommend anticoagulants for women with previous pregnancy loss without antiphospholipid antibodies 5

Risk Stratification Algorithm

Step 1: Assess for VTE History

• If prior VTE (unprovoked or hormonal-associated): Recommend antepartum and postpartum LMWH prophylaxis 1
• If prior VTE with temporary non-hormonal provocation (surgery, trauma): Suggest against antepartum prophylaxis but recommend postpartum prophylaxis 1

Step 2: Screen for Thrombophilia (if not already done)

• Test for antithrombin deficiency, factor V Leiden, prothrombin gene mutation, protein C/S deficiency 1
• High-risk thrombophilias warrant prophylaxis; low-risk thrombophilias do not 1

Step 3: Evaluate for Antiphospholipid Syndrome

• Screen women with recurrent early pregnancy loss (≥3 miscarriages before 10 weeks) or late pregnancy complications for antiphospholipid antibodies 1
• Do NOT routinely screen for inherited thrombophilia in women with pregnancy complications alone 1

Step 4: Consider Other Myeloproliferative Disorders

• In women with persistently elevated platelets and IUFD history, test for essential thrombocythemia with JAK2 V617F mutation 6, 7
• Aspirin (not LMWH) is the primary therapy for essential thrombocythemia in pregnancy 1, 6

Safety Profile of LMWH in Pregnancy

Maternal safety:

• LMWH prophylaxis does not increase major antepartum hemorrhage (0.2% with LMWH vs 0.6% without) or peripartum hemorrhage (2.5% vs 3.0%) 1
• No increased risk of osteopenia or osteoporotic fractures with antepartum LMWH 1

Fetal safety:

• Available data from published literature and postmarketing reports have not shown a clear association between LMWH and adverse developmental outcomes 2
• LMWH does not cross the placenta and is considered safe for the fetus 2

Common Pitfalls to Avoid

• Do not prescribe LMWH based solely on IUFD history without documented thrombophilia, VTE history, or antiphospholipid syndrome—the burden of daily injections throughout pregnancy is not justified by the evidence 3, 4
• Do not confuse thrombophilia screening indications: Screen for antiphospholipid antibodies in recurrent early pregnancy loss, but do NOT routinely screen for inherited thrombophilia based on pregnancy complications alone 1
• Do not use the same prophylaxis strategy for all thrombophilias: High-risk thrombophilias (antithrombin deficiency, homozygous mutations) require different management than low-risk thrombophilias 1
• Discontinue LMWH at least 24 hours before planned delivery or neuraxial anesthesia to minimize bleeding risk 1

Strength of Evidence

The recommendation against routine LMWH for isolated IUFD is based on high-quality randomized controlled trials from 2015 and 2012 showing no benefit 3, 4. The American Society of Hematology 2018 guidelines provide strong recommendations for LMWH in women with prior VTE but do not support its use for isolated pregnancy complications without thrombotic history 1.