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Clinical management of women with a history of adverse

pregnancy outcomes (ie, recurrent early pregnancy

loss, severe pre-eclampsia, placental abruption, and

unexplained fetal growth restriction or stillbirth) is a

challenging area in obstetrics because of the paucity

of evidence-based preventive therapies. In the face

of emotionally charged requests for preventive treatment

by women with adverse pregnancy outcomes,

clinicians are often tempted to provide non-evidencebased

therapies that might seem to be both biologically

plausible and of minimum harm.

In the 1990s, epidemiological d ata emerged showing an

association between genetic thrombophilias and adverse

pregnancy outcomes.1,2 The proposed pathophysiological

mechanism linking maternal prothrombotic tendencies

with adverse pregnancy outcomes is through placental

insuffi ciency caused by microvascular or macrovascular

thrombosis of this crucial maternal–fetal interface. This

concept led researchers to investigate low-molecularweight

heparin as a potential treatment to reduce

placental thrombosis and thereby reduce adverse

pregnancy outcomes. Early studies showed promising

results3,4 and, despite the absence of high-quality

evidence, clinicians and guideline committees5 quickly

adopted use of these drugs. However, subsequent higher

quality randomised clinical trials6,7 were unable to replicate

the success of earlier research.

The Thrombophilia in Pregnancy Prophylaxis Study

(TIPPS),8 undertaken by Marc Rodger and colleagues

and reported in The Lancet, is the fi rst large international

randomised controlled trial designed to resolve the

clinical equipoise of the eff ect of antepartum lowmolecular-

weight heparin (dalteparin) on adverse

pregnancy outcomes in women at the highest risk of

these outcomes (ie, women with both thrombophilia

and a history of either adverse pregnancy outcomes or

venous thromboembolism). The results of this study

are convincingly negative: following randomisation

of 292 women, antepartum dalteparin did not

signifi cantly reduce the incidence of adverse pregnancy

outcomes, the trial’s primary outcome, recorded in

25 of 146 women (17·1%) in the dalteparin group versus

27 of 143 (18·9%) in the control group (risk diff erence

–1·8%, 95% CI –10·6 to 7·1). The results were consistent

across the wide range of clinically important events that

comprised the composite primary outcome (severe or

early-onset pre-eclampsia, small-for-gestational-age

infants [<10th percentile], pregnancy loss, or venous

thromboembolism); in both intention-to-treat and ontreatment

analyses; and across pre-planned subgroup

analyses. From a patient safety perspective, although

no diff erences in major bleeding or bone mineral density

were recorded, dalteparin was associated with an

increase in minor bleeding, abnormal