Summary Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0·74–34·40); early pregnancy loss (ORs, 1·40–6·25); late pregnancy loss (ORs, 1·31–20·09); pre‐eclampsia (ORs, 1·37–3·49); placental abruption (ORs, 1·42–7·71) and intrauterine growth restriction (ORs, 1·24–2·92). Low‐dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1·62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Chronic venous disease of the legs occurs commonly in the general population in the Western world. Estimates of the prevalence of varicose veins vary widely from 2-56% in men and from 1-60% in women. These variations reflect differences in variability of study populations including age, race and gender, methods of measurement and disease definition. Definitions of chronic venous disease may rely on reports of varicose veins by study participants, based on self-diagnosis or recall of a diagnosis, or on a standardized physical examination. Venous ulceration is less common, affecting approximately 0.3% of the adult population. Age and pregnancy have been established as risk factors for developing varicose veins. Evidence on other risk factors for venous disease is inconclusive. Prolonged standing has been proposed, but results of studies should be interpreted with caution given the difficulty in measuring levels of posture. Obesity has been suggested as a risk factor in women, but appears to be an aggravating factor rather than a primary cause. Other postulated risk factors include dietary intake and smoking, but evidence is lacking. Longitudinal studies using standardized methods of evaluation are required before the true incidence of chronic venous disease and associated risk factors can be determined.

Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

The existing evidence supports a positive association between exposure to POS tobacco promotion and smoking. This review provides evidence to support the continuation of POS tobacco display bans in those jurisdictions where such legislation has been introduced and strengthens the evidence encouraging similar policies in jurisdictions without a POS display ban.