Prophylaxis for Venous Thromboembolic Disease in Pregnancy and the Early Postnatal Period

Background: Venous thromboembolic disease (TED), although rare, is a major cause of maternal mortality and morbidity, hence methods of prophylaxis are often used for women at risk. This may include women delivered by caesarean section, those with a personal or family history of TED and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry a risk of side effects, and as the risk of TED is low, it is possible that the benefits of thromboprophylaxis may be outweighed by harm. Current guidelines for clinical practice are based on expert opinion only, rather than high quality evidence from randomised trials.

Objectives: To determine the effects of thromboprophylaxis in women who are pregnant or have recently delivered and are at increased risk of TED on the incidence of venous TED and side effects of treatment.

Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009).

Selection Criteria: Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis.

Data Collection And Analysis: Two review authors extracted data independently and resolved any discrepancies by discussion.

Main Results: Sixteen trials met the inclusion criteria but only 13 trials, involving 1774 women, examining a range of methods of thromboprophylaxis, contributed data for the outcomes of interest. Four of them compared methods of antenatal prophylaxis: low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) (two studies), and heparin versus no treatment (two studies). Eight studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch with unfractionated heparin; four compared heparin with placebo; and the other three compared UFH with LMWH. One study examined prophylaxis in the postnatal period.The small number of statistically significant findings in this review are largely derived from trials which are not of high methodological quality. It was not possible to assess the effects of any of these interventions on most outcomes, and especially on rare outcomes such as death, TED and osteoporosis, because of small sample sizes and the small number of trials making the same comparisons.There was some evidence of side effects associated with thromboprophylaxis.

Authors' Conclusions: There is insufficient evidence on which to base recommendations for thromboprophylaxis during pregnancy and the early postnatal period. Large scale randomised trials of currently-used interventions should be conducted.