Department of Clinical Haematology Clinical Guideline: Pregnancy in patients with sickle cell disease HN-510b Introduction Pregnancies in patients with sickle cell disease and thalassaemia are associated with an increased risk of complications for both mother and neonate. Women with sickle cell anaemia have increased rate of pre-eclampsia compared with the unaffected pregnant women; the rates of stillbirth, spontaneous abortion, premature delivery and intrauterine growth retardation are all also increased. The high-risk nature of pregnancies in these women necessitates multidisciplinary team management. Pregnant women with a major haemoglobin disorder should be jointly managed by the haemoglobinopathy clinic and the high risk obstetric service (including obstetricians, obstetric physician and anaesthetists) as soon as pregnancy is confirmed. To which patients does this protocol apply? This protocol is principally aimed at patients homozygous for HbS (sickle cell anaemia), or compound heterozygotes for HbS and HbC, β0 thalassaemia, HbE, HbD and Hb O-Arab (all sickling diseases of varying severity). Note that patients who are carriers of βS (sickle cell trait) are not expected to have complications secondary to their haematological condition, and are not considered further in this protocol. Pregnancy in patients with thalassaemia major and intermedia is considered in a separate protocol. Summary of practice points • Management is coordinated by haematology (Dr Wale Atoyebi’s clinic) but all patients must be referred to High Risk Obstetrics at the earliest opportunity (in Oxford, the Silver Star Unit (Miss Catherine Greenwood, Miss Deborah Harrington and Dr Lucy Mackillop). • Pre-conception management: Optimize end-organ function and long term management. Counsel both parents with respect to risks to mother (esp cardiac) and child. Exclude pulmonary hypertension prior to pregnancy. Start 5 mg folic acid once trying to conceive, if not already taking. • Perform patient and partner screening antenatally whenever possible (contact: Jenny Eglinton, Molecular Haematology Lab, tel 01865 572769) • Refer all women with potentially affected fetuses for counselling and consideration of antenatal diagnostics (contact: Annie Roberts, prenatal screening coordinator, level 2 Women’s Centre, tel 01865 221087) Document number S24 Version 1.0 Page 1 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology • Withdraw hydroxycarbamide, iron chelation agents and ACEi/angiotensin receptor blockers from conception planning until breast-feeding is completed. • Exchange transfusion followed by top-up transfusion to lower the HbS percentage should be discussed with all patients who have had previously complicated pregnancies, those with a history of stroke or multiple chest crises, and those normally on hydroxycarbamide. • Avoid non-steroidal anti-inflammatories in the second and third trimesters; use paracetamol +/- opiates as required for painful crises. • Continue penicillin and folic acid (5mg/day) throughout pregnancy • Give low dose (75mg) aspirin daily from week 12 of gestation • Give thromboprophylaxis antenatally if at high risk of VTE • Follow-up monthly in haematology clinic for the first two trimesters, and fortnightly thereafter • Outpatient clinical assessment to document general well-being, symptoms of anaemia, features suggestive of pre-eclampsia (BP, urine dip) and infection (MSU) as well as monitoring of FBC, LFT, renal function and assessment of titre of any red cell antibody. • Caesarean section is indicated for obstetric reasons only. Epidural anaesthesia should be considered early. • Venous thromboembolism prophylaxis is required post partum for at least 7 days. Document number S24 Version 1.0 Page 2 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology 1. Pre-pregnancy care and counselling Plans for pregnancy and contraception are key components of the long term care of women with major haemoglobin disorders and should be documented at each clinic visit. Where possible, pregnancy should be deferred until the woman’s general haemoglobinopathy management is optimal. Preconception screening to assess for end organ damage should include: • Echocardiography to exclude pulmonary hypertension (a contraindication to pregnancy) • Blood pressure and urinalysis • Retinal screening • Screening for iron overload – iron chelation is advised pre-conception for women who are significantly iron overloaded. • Screening for red cell antibodies. Vaccination The patient’s vaccination schedule should be up to date: vaccination is recommended against hepatitis B; pneumococcal vaccinations are due every five years; and the HIb /conjugated menC vaccines may be given as single dose if this has not been given before. Where the patient is already pregnant when seeking medical advice, live attenuated vaccines should be deferred until after delivery. Hydroxycarbamide (hydroxyurea) is contraindicated in pregnancy and should be withdrawn three months prior to conception. For patients who are normally maintained on hydroxyurea to control frequent crises, consideration should also be given to the use of exchange transfusion during the pregnancy as a holding measure in the absence of Hydroxycarbamide. Note that pregnancies have been completed successfully without fetal malformation where there has been exposure to hydroxycarbamide; exposure alone is therefore not an indication for termination. However, referral should be made to prenatal diagnosis for fetal assessment. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers used for the management of hypertension and renal disease should be withdrawn prior to conception; they are associated with renal and cardiac malformations and fetal loss. Iron chelation with desferrioxamine, deferiprone and deferasirox should also be withdrawn prior to conception. Counselling pre-pregnancy Patients should be advised of the risks to both mother and child of pregnancy. Specifically patients should be advised: Document number S24 Version 1.0 Page 3 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology • • • • • • The risk of having a child affected by a haemoglobin disorder (partner screening advised) The increased risk of fetal complications including growth restriction, premature delivery and stillbirth The increased risk of Caesarean section; The increased risk of sickle crises during pregnancy (e.g. precipitated by nausea/vomiting) The expected worsening of anaemia during pregnancy The increased risk of pre-eclampsia Patients with pulmonary hypertension are at particular risk, and may not tolerate the increase in stroke volume/cardiac output required by pregnancy and labour. Such patients should be advised of the risk to their own health of embarking upon pregnancy. 2. Antenatal screening and prenatal diagnostics Partner screening should be performed where possible. This should ideally take place prior to conception by the haemoglobinopathy service or general practitioner, or may be performed as part of the national screening programme at booking. Haemoglobin electrophoresis and IEF are performed specifically with a view to detecting: • β thalassaemia • O-Arab • HbC • D-Punjab Any of the above in the partner of a patient with sickle cell anaemia should prompt the offer of prenatal diagnostics. Chorionic villus sampling can be performed after week 10 of pregnancy; amniocentesis can be done from week 14. Both procedures have miscarriage risk of approximately 0.5-1%. In Oxford, this is coordinated by Annie Roberts (prenatal screening coordinator). Annie Roberts will usually be alerted to women with ‘at risk’ pregnancies by the laboratory haemoglobinopathy screening service, but may also be contacted by clinicians to discuss screening (ext 21087). Document number S24 Version 1.0 Page 4 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology 3. Booking and initial assessment of the pregnant patient Initial appointment: • clarify whether partner testing and prenatal diagnosis has been discussed/taken place • document baseline oxygen sats and BP • dip urine and send MSU for culture • check baseline renal function, protein/creatinine ratio, liver function tests, iron status (ferritin) • perform extended red cell phenotype if not previously done in house, and assess for the presence of red cell antibodies. 4. Ongoing management Women should be seen monthly from booking to 24 weeks; then fortnightly from 24 weeks to 36 weeks; then weekly to term. Women with sickle cell anaemia have an increased risk of: • Pregnancy induced hypertension and Pre-eclampsia • Fetal compromise • Asymptomatic urinary tract infection Therefore, urinalysis, MSU for culture, and blood pressure should be checked at every visit, with FBC, LFTs and renal function monthly. Upward trends in blood pressure and the development of proteinuria should be discussed the same day with the Silver Star team/obstetric physicians. Microbiological evidence of urinary tract infection should be treated according to the Trust’s antibiotic guidelines (see ouh.oxnet.nhs.uk) If red cell allo-antibodies are detected on initial screening, repeat titrations should be performed fortnightly from 16 weeks’ gestation. USS of the fetus should be performed: • At 12 weeks to confirm gestational age, and to permit nuchal translucency measurement • At 20 weeks (anomaly scan) • Uterine artery Doppler assessment at 23 weeks • At 28, 32 and 36 weeks to monitor fetal growth • Fetal well-being should be assessed sonicaid/cardiotocography during maternal admissions for any complication Document number S24 Version 1.0 Page 5 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology Additional management points • Penicillin V 250 bd should be continued throughout pregnancy • Folic acid 5mg od should be continued throughout pregnancy • There is no indication for iron supplementation unless iron deficiency is formally demonstrated as many patients will have some degree of iron loading • An individualized management plan for painful crises should be discussed with and documented for each patient – note that nonsteroidal antiinflammatories are contraindicated, but opiates are acceptable for pain relief • Low dose aspirin (unless patient sensitive to aspirin) from 12 weeks’ gestation is recommended for patients with sickle cell anaemia due to the increased risk of pre-eclampsia. • VTE risk assessment should be performed at booking, and during any hospital admission or change in patient circumstances. Prophylaxis with low molecular weight heparin should be prescribed if considered at high risk. 5. Transfusion of patients with sickle cell anaemia • Routine transfusion is not required during pregnancy • Symptomatic anaemia or Hb<60g/l may be indications for top-up transfusion • Exchange transfusion is likely to be used early in pregnancy for women with previously complicated pregnancies, previous stroke, chest crises, or the requirement for hydroxycarbamide to control sickle crises; decisions to exchange will be made in conjunction with each individual patient at their first clinic appointment after pregnancy is confirmed. • Exchange transfusion will usually be followed by monthly top-up transfusion to maintain an HbS level <30% • Transfusion to 100-110g/l is acceptable; higher Hb levels should be avoided due to the risk of hyperviscosity • Blood should be subject to extended matching, and should be sickle negative, CMV negative. 6. Management of complications of sickle cell disease in pregnancy Women should be admitted to the antenatal ward for complications experienced in the second and third trimesters to allow access to expert nursing care and fetal monitoring. Painful crises should be treated as in the non-pregnant patient, with the exception of avoidance of non-steroidal agents. Women should be reassured regarding the transplacental passage of opioids: only women with opioid dependence are likely to experience problems with fetal opiate withdrawal symptoms after delivery. Prophylactic anticoagulation is advised while an inpatient. Acute complications such as chest crisis should be managed as in the non-pregnant patient. Document number S24 Version 1.0 Page 6 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology 7. Late antenatal care and delivery An anaesthetic assessment is indicated in the third trimester in the light of potentially complicated labour and likely pre-existing end organ damage. This should be arranged through the obstetric service. • • • • • Spontaneous vaginal delivery is expected in the absence of any obstetric indication to the contrary. Nitrous oxide may be used for short periods for pain relief without precipitating a crisis. Since a high rate of requirement for Caesarean section is recognized, consideration of epidural anaesthesia is encouraged Continuous fetal heart monitoring is advised to detect hypoxia (commoner in the fetuses of sickle cell patients). In the event of Caesarean section, exchange is not typically required, and topup transfusion is needed only in cases of severe anaemia. Prolonged labour and associated dehydration may increase the risk of developing a sickle crisis. Intravenous hydration should be initiated if oral hydration is not adequate to maintain an intake of 3l/24hr in the context of prolonged labour. Increased oxygen demands during labour require the monitoring of maternal oxygen saturations by oximetry. 8. Postpartum care There is an increased risk of postpartum haemorrhage, tissue hypoxia and hypovolaemia, thromboembolism and infection, making this a high risk period for women with sickle cell anaemia. • • • • • Ensure 4 hourly observations until the mother is mobile Provide thromboprophylaxis with daily subcutaneous low molecular weight heparin for 7 days post discharge in the case of uncomplicated vaginal delivery Provide LMWH prophylaxis for 6 weeks if other risk factors for VTE. There is no indication for routine antibiotic prophylaxis post partum (beyond ongoing asplenic prophylaxis), but suspected infection should be treated promptly according to OUH guidelines. Oral iron chelators (deferiprone and deferasirox), hydroxycarbamide, and ACE inihibitors/angiotensin receptor antagonists should be withheld while breastfeeding. Desferrioxamine is safe if needed during the period of breastfeeding. Cord blood should be sent for haemoglobin electrophoresis; if results are equivocal, the test should be repeated at 6 weeks of age. (Note that the high level of HbF may give a false negative result on the sickle solubility test.) Document number S24 Version 1.0 Page 7 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Oct 2012 Pregnancy in SCD Department of Clinical Haematology 9. Contraception Progesterone-only contraception is the first choice contraceptive for women with sickle since it is without clinically significant adverse effects and may reduce crisis frequency. The combined pill may be associated with increased risk of thrombosis. Documentation and acknowledgements: Royal College of Obstetricians and Gynaecologists Green-top guideline no.61: Management of Sickle Cell Disease in Pregnancy, July 2011 The Obstetric management of sickle cell disease Howard J et al. Best Practice and Research Clinical Obstetrics and Gynaecology 2012 26: 25-36 Sickle cell disease in pregnancy. Oteng-Ntim E, Chase AR, Howard J, et al. Obstetrics, Gynaecology and Reproductive Medicine 18:10 272-278 Standards for the clinical care of adults with sickle cell disease in the UK. Sickle Cell Society 2008, and references therein. Authors: D Hay, SpR in Haematology; W Atoyebi, Clinical Lead for Haemoglobinopathies; L Mackillop, Specialist Obstetric Physician Review Name Wale Atoyebi Revision Pre-peer review Date Jan 2013 Version 1.0 Document number S24 Version 1.0 Page 8 of 8 Authorised by:.W Atoyebi This is a controlled document and therefore must not be changed Review date Jan 2015 Oct 2012 Pregnancy in SCD