Description of the condition

Bleeding disorders can pose significant challenges during pregnancy and childbirth. Pregnancy is a hypercoagulable state and may mask or balance the bleeding risk (if mild). Many bleeding disorders tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery. However, some do not correct or return relatively quickly to the pre‐pregnancy levels in the postpartum period, thus requiring specific measures to prevent maternal and foetal bleeding complications during childbirth. Von Willebrand disease (VWD), haemophilia A and B, factor XI (FXI) and factor VII (FVII) deficiency account for almost 90% of the inherited bleeding disorders, whereas deficiency in fibrinogen, prothrombin factor (FIII), factor V (FV), factor X (FX), factor XIII are relatively rare (Chi 2007). Idiopathic thrombocytopenic purpura (ITP) is a commonly acquired bleeding disorder during pregnancy and accounts for 3% to 4% of the cases of thrombocytopenia detected at this time (Gill 2000); whereas HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome is a rarer acquired bleeding disorder during pregnancy, occurring in approximately one to two per 1000 pregnancies (Geary 1997).

• Von Willebrand disease is caused by a quantitative or qualitative defect in Von Willebrand factor (VWF). An increase in VWF (with levels in blood plasma up to normal plasma levels) is often seen during pregnancy in women with VWD (except type 3), but intrapatient variability is very wide (Conti 1986). A drastic fall in VWF following delivery in women with VWD causes these women to be prone to primary and secondary postpartum haemorrhage (PPH) (James 2009).

• Congenital haemophilias are X‐linked recessive bleeding disorders that result from deficiencies of the coagulation factors VIII (FVIII) and IX (FIX). Most female carriers of haemophilia have levels of FVIII (or FIX) within the normal range and are therefore protected against significant bleeding problems in day‐to‐day life (Giangrande 2009). Pregnant carriers of haemophilia A usually have low levels of FVIII at the beginning of pregnancy, but have almost normal levels of FVIII by the third trimester. In normal pregnancy, FIX levels do not rise significantly (Stirling 1984). Women with levels of FVIII (or FIX) under 50% (less than 0.50 international units (IU)/millilitre (mL)) are at increased risk of bleeding when facing haemostatic challenges (Lusher 1978). Female carriers of haemophilia A are at an increased risk of haemorrhagic complications, both early and late PPH, because of the rapid fall in the increased pregnancy‐induced maternal clotting factor levels (FVIII) after delivery. The incidence of early and late PPH is increased among haemophilia A carriers (22% and 11%, respectively) (Kadir 1997) compared with the general population (5% and 0.7%, respectively) (Lee 1981). Risk of head bleeding in babies (cephalohaematoma, intracranial haemorrhage) is 3%, 64% and 15% following normal delivery, vacuum extraction and caesarean section (c‐section) respectively (Ljung 1994).

• Factor XI deficiency (haemophilia C) and FVII deficiency are very rare inherited bleeding disorders in the general population, but FXI deficiency more commonly occurs in individuals of the Ashkenazi Jewish population compared to other populations (Bolton‐Maggs 1988). Homozygous and compound heterozygous individuals with FXI and FVII deficiency develop haemorrhagic manifestations; heterozygous individuals are usually asymptomatic but may present with profuse bleeding. Clinical prototypes vary from mild to severe and do not correlate with FXI and FVII levels. The levels of FXI and FVII do not change during pregnancy and there is a poor correlation between the level of FXI and bleeding tendency (Bolton‐Maggs 1988). For both FXI and FVII deficiencies, the bleeding tendency is likely to be associated with levels of factor less than 15%, and varies in the same individual following different haemostatic challenges. As a consequence of the unpredictable nature of these diseases, their management during pregnancy and childbirth is quite difficult.

• Inherited  fibrinogen abnormalities, factor II, FV, FX and FXIII deficiencies are the rarest bleeding disorders; bleeding tendencies are low in heterozygous groups but life‐threatening in the homozygous group, and mostly occurring as PPH (Bolton‐Maggs 1988; Fadel 1989).

• Congenital platelet dysfunction disorders, being autosomal recessive disorders, are rare. Better characterized defects are those in the platelet GPIb complex (Bernard‐Soulier Syndrome) or the GPIIb‐IIIa complex (Glanzmann thrombasthenia) or in the platelet secretion or thromboxane synthesis. Bleeding tendencies are severe in Bernard‐Soulier Syndrome and Glanzmann thrombasthenia, usually requiring platelet transfusion. Bleeding is milder in platelet dysfunction disorders, which are due to abnormal platelet secretion or thromboxane synthesis, but can be life‐threatening following surgery or trauma (George 1990; Peng 1991).

• A common cause of acquired bleeding disorder in pregnancy is ITP which occurs in 1000 to 2000 deliveries (Burrows 1990). The risk of spontaneous bleeding at birth in women with ITP is low and occurs particularly if the platelet count decreases to less than 20,000/µL (Webert 2003). The frequency of neonatal allo immunisation thrombocytopenia (NAIT) is estimated at one to two cases per 1000 deliveries (Blanchette 1990). This disorder develops in foetal life, with 25% to 50% of foetal intracranial haemorrhages detectable on prenatal ultrasound prior to the onset of labour (Herman 1986).

• The HELLP syndrome occurs in 10% to 20% of cases with severe pre‐eclampsia (Geary 1997). Maternal mortality in pregnancy associated with HELLP syndrome is 1.1% (Sibai 1993) and the perinatal mortality is 34% before 32 weeks gestation, and 8% after this (Gul 2005). A total of 30% of HELLP syndromes develop after birth, the majority within the first 48 hours with the time of onset ranging from a few hours to seven days following delivery (Barton 2004).

• More common but still very serious maternal complications are placenta abruptio, disseminated intravascular coagulation (DIC) and subsequent severe PPH; whereas, prematurity, intrauterine growth restriction (IUGR) and abruptio placenta are the leading causes of neonatal death (Magann 1999). Hepatic rupture has a perinatal mortality that can reach 80% (Mihu 2007), the majority of which are observed during the antenatal period.

Pregnant women with bleeding disorders require a multidisciplinary approach, especially for those pregnant women with severe and rare bleeding disorders. The delivery is planned at a unit where the necessary expertise in the management of bleeding disorders is present and resources for laboratory testing and clotting factor treatments are readily available (Bolton‐Maggs 2004).

During antenatal checkups in women with inherited bleeding disorders, affected foetuses can be diagnosed by non‐invasive or invasive prenatal diagnostic methods such as analysis of foetal DNA in maternal blood using digital polymerase chain reaction or a relative mutation dosage approach (Tsui 2011) during early pregnancy. Relevant coagulation factor levels should be checked at pregnancy diagnosis, at 28 and at 34 weeks of gestation, and also prior to any invasive procedure, which allows treatment to be managed in acute situations when urgent assays may be difficult to obtain (Street 2008).

Prevention of bleeding is by undertaking prophylactic treatment, such as recombinant or plasma‐derived clotting factor concentrates, tranexamic acid or desmopressin, when factor levels are less than 50 IU/decilitre (dL) for FVIII, FIX, Von Willebrand factor antigen (VWF:Ag) and Von Willebrand factor activity (VWF:Ac) or less than 70 IU/dL for FXI to cover invasive procedures, labour, delivery; treatment is usually continued for at least three days following vaginal delivery and at least five days following c‐section (Ljung 1994).

In pregnant women with ITP, most experts opine that a platelet count in the range of 50,000/μl for vaginal delivery and 80,000/μl for epidural anaesthesia and c‐section during and after delivery is adequate (Cines 2005; Stavrou 2009).

The optimal mode of delivery in women with bleeding disorders is chosen on an individual case basis. The risks and benefits involved in relation to both mother and foetus in each mode of delivery are discussed by a multidisciplinary team consisting of obstetricians, haematologists, paediatricians and anaesthesiologists (Chic 2008). In women with bleeding disorders, controlled delivery of the foetus by planned c‐section has been suggested to reduce the risk of intracranial haemorrhage (ICH) by an estimated 85% compared with vaginal delivery, whereas maternal mortality and morbidity are not significantly different from those observed in vaginal delivery (James 2010).

Bleeding complications during delivery are estimated at 1% to 4% (intracranial haemorrhage, cephalo‐haematoma) in infants with inherited bleeding disorders or ITP, and more commonly observed with traumatic delivery.

Description of the intervention

Pregnancy and childbirth management in women with bleeding disorders is a multidisciplinary approach consisting of obstetricians, haematologists, anaesthesiologists and neonatologists. Delivery is conducted in centres where laboratory testing and clotting factor concentrates are readily available. Optimal management of delivery has to take into account the health needs and goals for both the mother and the newborn. indeed, the debate about the delivery modality optimizing the risk‐to‐benefit ratio for the mother and the newborn is fully open. While it is impossible to separate the two when making treatment choices, it might be appropriate to attempt to separate them when describing the intervention.

Certainly, one goal is to achieve delivery by the least traumatic method, and early recourse to c‐section can be considered to minimise the risk of bleeding complications for both mother and newborn. Caesarean section is safer for the foetus and riskier for the mother, although the latter has not been proven in the context of bleeding disorders (James 2010). Prolonged labour should be avoided whenever possible. Maternal genital and perineal trauma should be minimised in order to reduce the risk of excessive bleeding at delivery (Kadir 1998; McMahon 2001).

Conversely, vaginal delivery is considered a safe mode of delivery in women with bleeding disorders, and the indication for undertaking a c‐section is an obstetric decision. Vaginal delivery also avoids surgical morbidity and anaesthesia‐related complications (Lee 2006). Special attention to haemostasis is required to minimise bleeding during c‐section.

For both c‐section and vaginal delivery, administration of neuraxial or general anaesthesia are considered safe. In women with, or carriers of, bleeding disorders, the risk of spinal or epidural haematoma following administration of neuraxial anaesthesia may be increased with potential for permanent neurological injury (Vandermeulen 1994). The decision for neuraxial anaesthesia is individualised and the procedure is better performed after an optimum level of deficient clotting factor is achieved. When there is concern about the increased risk of spinal or epidural haematoma, patient‐controlled analgesia with fentanyl is an alternative option (Campbell 2003). Caesarean section under general anaesthesia is considered in cases where neuraxial analgesia is contraindicated.

Instrumental delivery with low forceps is permissible, delivery by vacuum extraction or mid‐cavity or rotational forceps delivery is not recommended and episiotomies and foetal scalp electrodes are tentatively avoided (Ljung 1994).

Prophylactic administration of a uterotonic drug (oxytocin, ergometrine, misoprostol, carboprost) along with active management of the third stage of labour are the main strategies to prevent PPH.

A deficient coagulation level persisting during pregnancy must be corrected to a safe level by supplementation in order to prevent bleeding during childbirth. If the goal is to normalize the haemostatic level before the procedure and to maintain it for at least five to seven days following either vaginal or c‐section delivery, prophylactic replacement therapy in severe bleeding disorders and desmopressin in mild bleeding disorders is considered to prevent PPH. Lack of data from the literature in relation to foetuses with rare bleeding disorders and knowledge is extrapolated from experience of newborns with common bleeding disorders such as haemophilia (Ljung 1994).

Treatment of newborns affected, or at risk of being affected, by congenital coagulopathies are not the object of this review.

How the intervention might work

Choices regarding the modality of delivery, use of instruments, type of anaesthesia, administration of prophylactic factor concentrates or treatment or active bleeding during obstetrical procedures are all interventions aimed at preventing, reducing or treating obstetrical bleeding complications. Evidence about the risk‐benefit ratio for the mother and the fetus is scanty, and no strong recommendations are available in the filed. The safest method of delivery for foetuses at risk is controversial (James 2010; Towner 1999). Low forceps delivery is considered less traumatic compared to c‐section when the head is deeply engaged in the pelvis and an easy outlet delivery is anticipated (Kadir 1998; McMahon 2001). Any, or different combinations of these interventions, can be associated with clinically significant outcomes. This review will focus on the specific role of vaginal versus c‐section delivery.

Why it is important to do this review

At present, there is an ongoing debate about the best way to deliver babies in women with, or at risk of, congenital bleeding disorders. The evidence for vaginal versus surgical delivery is limited. This review will investigate the safety and efficacy associated with the mode of delivery in women with bleeding disorders and carriers, taking into account the effects on both the mother and the foetus.This is an update of a Cochrane review first published in 2015 (Karanth 2015)