In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Classification of evidence levels (1++ to 4) and grades of recommendations (A-D) are defined at the end of the "Major Recommendations" field.
What Is the Importance of Planning Pregnancy and How Can Outcomes for the Woman and Baby Be Improved?
D - From adolescence, the intentions of women with sickle cell disease (SCD) regarding pregnancy and contraception should be documented at each contact with their sickle care team.
D - Women with SCD should be seen preconceptually by a sickle specialist to receive information about how SCD affects pregnancy and how pregnancy affects sickle cell disease, and how to improve outcomes for mother and baby. This consultation should include optimisation of management and screening for end organ damage.
The assessment for chronic disease complications should include:
- Screening for pulmonary hypertension with echocardiography. The incidence of pulmonary hypertension is increased in patients with SCD and is associated with increased mortality. A tricuspid regurgitant jet velocity of more than 2.5 m/second is associated with a high risk of pulmonary hypertension. Screening should be performed if this has not been carried out in the last year.
- Blood pressure and urinalysis should be performed to identify women with hypertension and/or proteinuria. Renal and liver function tests should be performed annually to identify sickle nephropathy and/or deranged hepatic function.
- Retinal screening. Proliferative retinopathy is common in patients with SCD, especially patients with sickle-haemoglobin C disease (HbSC), and can lead to loss of vision. There is no randomised evidence on whether routine screening should be performed or if patients should be screened only if they experience visual symptoms, but we recommend that women are screened preconceptually.
- Screening for iron overload. In women who have been multiply transfused in the past or who have a high ferritin level, T2* cardiac magnetic resonance imaging may be helpful to assess body iron loading. Aggressive iron chelation before conception is advisable in women who are significantly iron loaded.
- Screening for red cell antibodies. Red cell antibodies may indicate an increased risk of haemolytic disease of the newborn. [Evidence level 4]
What Is the Importance of Genetic Screening and What Procedure(s) Are Involved?
D - Women and men with SCD should be encouraged to have the haemoglobinopathy status of their partner determined before they embark on pregnancy. If identified as an 'at risk couple', as per National Screening Committee guidance, they should receive counselling and advice about reproductive options.
What Is the Importance of Antibiotic Prophylaxis and Immunisation?
D - Penicillin prophylaxis or the equivalent should be prescribed.
D - Vaccination status should be determined and updated before pregnancy.
People who are allergic to penicillin should be recommended erythromycin.
Women should be given Haemophilus influenza type b and the conjugated meningococcal C vaccine as a single dose if they have not received it as part of primary vaccination. The pneumococcal vaccine (Pneumovax®, Sanofi Pasteur MSD Limited, Maidenhead, UK) should be given every 5 years. [Evidence level 1]
Hepatitis B vaccination is recommended and the woman's immune status should be determined preconceptually. Women with SCD should be advised to receive the influenza and 'swine flu' vaccine annually. Penicillin prophylaxis and vaccinations are usually monitored and administered in primary care, but should be reviewed by the specialist haematologist/obstetrician during pregnancy. [Evidence level 4]
What Vitamin Supplements Should Be Given?
D - Folic acid (5 mg) should be given once daily both preconceptually and throughout pregnancy.
What Medications Should Be Reviewed Preconceptually?
D - Hydroxycarbamide (hydroxyurea) should be stopped at least 3 months before conception.
D - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be stopped before conception.
D - Antenatal care should be provided by a multidisciplinary team including an obstetrician and midwife with experience of high-risk antenatal care and a haematologist with an interest in SCD.
D - Women with SCD should undergo medical review by the haematologist and be screened for end organ damage (if this has not been undertaken preconceptually).
D - Women with SCD should aim to avoid precipitating factors of sickle cell crises such as exposure to extreme temperatures, dehydration and overexertion.
D - Persistent vomiting can lead to dehydration and sickle cell crisis and women should be advised to seek medical advice early.
D - The influenza vaccine should be recommended if it has not been administered in the previous year.
Antenatal Haemoglobinopathy Screening
D - If the woman has not been seen preconceptually, she should be offered partner testing. If the partner is a carrier, appropriate counselling should be offered as early as possible in pregnancy – ideally by 10 weeks of gestation – to allow the option of first-trimester diagnosis and termination if that is the woman's choice.
What Medication Should Be Given During Pregnancy?
D - If women have not undergone a preconceptual review, they should be advised to take daily folic acid and prophylactic antibiotics (if not contraindicated). Drugs that are unsafe in pregnancy should be stopped immediately.
D - Iron supplementation should be given only if there is laboratory evidence of iron deficiency.
D - Women with SCD should be considered for low-dose aspirin 75 mg once daily from 12 weeks of gestation in an effort to reduce the risk of developing pre-eclampsia.
D - Women with SCD should be advised to receive prophylactic low-molecular-weight heparin during antenatal hospital admissions.
Non-steroidal anti-inflammatory drugs (NSAIDs) should be prescribed only between 12 and 28 weeks of gestation owing to concerns regarding adverse effects on fetal development.
What Additional Care Should Be Provided During the Antenatal Appointment?
D - Antenatal appointments for women with SCD should provide routine antenatal care as well as care specifically for women with SCD.
C - Blood pressure and urinalysis should be performed at each consultation, and midstream urine for culture performed monthly.
At each appointment, opportunities should be offered for information and education. The woman's housing and work circumstances should be reviewed, and interventions which may reduce the potential provocation of acute crises (e.g., improved heating, allowance for increased hospital visits) should be encouraged. Table 2 in the original guideline document outlines the recommended frequency and content of antenatal appointments for women with SCD.
What Is the Role of Blood Transfusion During Pregnancy?
A - Routine prophylactic transfusion is not recommended during pregnancy for women with SCD.
D - If acute exchange transfusion is required for the treatment of a sickle complication, it may be appropriate to continue the transfusion regimen for the remainder of the pregnancy.
A - Blood should be matched for an extended phenotype including full rhesus typing (C, D and E) as well as Kell typing.
The decision to recommend transfusion should be made by an experienced haematologist and obstetrician. Indications for transfusion are summarised in Table 3 of the original guideline document.
What Is the Optimal Management of Acute Painful Crisis During Pregnancy?
D - Women with SCD who become unwell should have sickle cell crisis excluded as a matter of urgency.
D - Pregnant women presenting with acute painful crisis should be rapidly assessed by the multidisciplinary team and appropriate analgesia should be administered. Pethidine should not be used because of the associated risk of seizures.
D - Women admitted with sickle cell crisis should be looked after by the multidisciplinary team, involving obstetricians, midwives, haematologists and anaesthetists.
D - The requirement for fluids and oxygen should be assessed, and fluids and oxygen administered if required.
D - Thromboprophylaxis should be given to women admitted to hospital with acute painful crisis.
What Are the Other Acute Complications of SCD and How Are They Treated?
D - All patients, carers, medical and nursing staff should be aware of the other acute complications of SCD, including acute chest syndrome (ACS), acute stroke and acute anaemia.
D - Each hospital should have a protocol in place for the management of ACS in pregnancy, including the use of transfusion therapy.
What Is the Optimal Timing and Mode of Delivery?
D - Pregnant women with SCD who have a normally growing fetus should be offered elective birth through induction of labour, or by elective caesarean section if indicated, after 38+0 weeks of gestation.
D - SCD should not in itself be considered a contraindication to attempting vaginal delivery or vaginal birth after caesarean section.
D - Blood should be cross-matched for delivery if there are atypical antibodies present (since this may delay the availability of blood), otherwise a 'group and save' will suffice.
What Is the Optimum Care and Place of Birth for a Woman with SCD?
D - Women with SCD should be advised to give birth in hospitals that are able to manage both the complications of SCD and high-risk pregnancies.
D - The relevant multidisciplinary team (senior midwife in charge, senior obstetrician, anaesthetist and haematologist) should be informed as soon as labour is confirmed.
D - Women should be kept warm and given adequate fluid during labour.
D - Continuous intrapartum electronic fetal heart rate monitoring is recommended owing to the increased risk of fetal distress which may necessitate operative delivery.
During labour, if oral hydration is not tolerated or is inadequate, intravenous fluids should be administered using a fluid balance chart to prevent fluid overload. Venous access can be difficult, especially if they have had multiple previous admissions, and as such anaesthetic review/intravenous access should be obtained early. The demand for oxygen is increased during the intrapartum period and the use of pulse oximetry to detect hypoxia in the mother is appropriate during labour. Arterial blood gas analysis should be performed and oxygen therapy instituted if oxygen saturation is 94% or less. [Evidence level 4]
Routine antibiotic prophylaxis in labour is currently not supported by evidence, but hourly observations of vital signs should be performed. A raised temperature (over 37.5ºC) requires investigation. The clinician should have a low threshold to commence broad-spectrum antibiotics.
What Is the Optimal Mode of Analgesia and Anaesthesia?
D - Women with SCD should be offered anaesthetic assessment in the third trimester of pregnancy.
D - Avoid the use of pethidine, but other opiates can be used.
D - Regional analgesia is recommended for caesarean section.
What Should Be the Optimum Care Post-Delivery?
D - In pregnant women where the baby is at high risk of SCD (i.e., the partner is a carrier or affected), early testing for SCD should be offered. Capillary samples should be sent to laboratories where there is experience in the routine analysis of SCD in newborn samples. This will usually be at a regional centre.
D - Maintain maternal oxygen saturation above 94% and adequate hydration based on fluid balance until discharge.
D - Low-molecular-weight heparin should be administered while in hospital and 7 days post-discharge following vaginal delivery or for a period of 6 weeks following caesarean section.
What Postpartum Contraceptive Advice Should Women Be Given?
B - Progestogen-containing contraceptives such as the progesterone only pill (Cerazette®, Organon Laboratories Ltd, Hoddesdon, UK), injectable contraceptives (Depo-Provera®, Pfizer Ltd, New York, USA) and the levonorgestrel intrauterine system (Mirena®, Bayer Schering Pharma AG, Berlin, Germany) are safe and effective in SCD.
D - Estrogen-containing contraceptives should be used as second-line agents.
Grades of Recommendations
A - At least one meta-analysis, systematic review or randomised controlled trial rated as 1++ and directly applicable to the target population; or
A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results
B - A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D - Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group
Classification of Evidence Levels
1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias
1– Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies or high-quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal
2– Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3 Non-analytical studies, e.g., case reports, case series
4 Expert opinion