However, it carries some risk of heparin-induced thrombocytopenia and osteopenia, which may lead to symptomatic vertebral fracture in Moreover, the pharmacokinetic changes of pregnancy result in a shorter half-life and lower peak plasma concentration of heparin compounds, with the need to titrate doses in order to keep the mid-interval aPTT (6 h post dose $ twice control values). Since both the risk of heparin- induced thrombocytopenia and the risk of osteoporosis are lower with LMWH than with UFH, the former is preferred as subcutaneous treatment during pregnancy. Pregnant women were excluded from participating in clinical trials evaluating NOACs. Given the rather low molecular weight of NOACs and data on placental transfer in rats, all NOACs are expected to cross the Hence, use of NOACs in pregnancy should be avoided. Limited data are available on the consequences of exposure to NOACs, but women inadvertently exposed to an NOAC in early pregnancy before diagnosis of pregnancy) can be reassured, since the risk of embryopathy seems low. In case of planned pregnancy, avoidance of NOACs should be considered (with switching to LMWH). Regarding breast-feeding, warfarin, in view of its characteristics (polar, non-lipophilic, and highly protein bound), can be considered safe since 2 reports showed that warfarin is not detected in breast milk and does not induce an anticoagulant effect in the breast-fed infant when breast-feeding mothers consume the drug.424,425 Acenocoumarol, which is commonly used in Europe, has similar properties.426,427 Use of UFH and LMWH in breast-feeding women appears safe. No clinical data on the effect of NOACs on breast-fed infants are available, and therefore the recommendation is against use these medications in breast-feeding women. A ow chart on how to manage women with AF during pregnancy is shown in Figure 8. Recommendations 45. 