Management of Sickle Cell Disease in Pregnancy

Management of sickle cell disease in pregnancy

Rashmi Sharma

ABSTRACT

Sickle cell anemia is an autosome linked recessive trait that can be transmitted from parents to the offspring whenboth the partners are carrier for the gene (or heterozygous). The disease is controlled by a single pair of allele, HbAand HbS. Out of the three possible genotypes only homozygous individuals for HbS (HbS, HbS) show the diseasedphenotype. The ability to predict the clinical course of SCD during pregnancy is difficult. It is mandatory to follow upthe patient closely from the very beginning i.e. from preconception to antenatal till labor. SCD is associated with bothmaternal and fetal complications and is associated with an increased incidence of perinatal mortality, prematurelabor, fetal growth restriction and acute painful crises during pregnancy.

Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved.

Keywords: Sickle cell anemia, Acute anemia, Hemoglobin, Pregnancy

INTRODUCTION

The term Sickle cell disease encompasses several differentsickle hemoglobinopathies. It includes sickle cell anemia(HbSS) and the heterozygous conditions of hemoglobin Sand other clinically abnormal hemoglobin. These includecombination with hemoglobin C (giving HbSC), combina-tion with beta thalassemia (giving HbSB thalassemia) andcombination with hemoglobin D, E or O-Arab. The patho-physiology of SCD is a consequence of polymerization ofthe abnormal hemoglobin in low-oxygen conditions, whichleads to the formation of rigid and fragile sickle-shaped redcells. Pregnancy with sickle cell disease needs to be takencare of very closely; from preconception to labor.2

PRECONCEPTION CARE

Women with SCD should be seen preconceptually bya sickle specialist to receive information about how SCDaffects pregnancy and how pregnancy affects sickle celldisease, and how to improve outcomes for mother andbaby. This consultation should include optimization ofmanagement and screening for end-organ damage. Women

with SCD should be encouraged to have the hemoglobinop-athy status of their partner determined before they embarkon pregnancy and they should receive appropriate coun-seling regarding the risk of having affected offspring.7

Management & treatment

Patients with SCD are hyposplenic and are at risk of infec-tion, in particular from encapsulated bacteria such as Neis-seria meningitides, Streptococcus pneumonia andHaemophilus influenzae. They should be given penicillinprophylaxis. In addition, women should be givenH. influenzae type b and the conjugated meningococcal Cvaccine as a single dose if they have not received it aspart of primary vaccination. Hepatitis B vaccination is rec-ommended and the woman’s immune status should bedetermined preconceptually. Women with SCD should beadvised to receive the influenza and ‘swine flu’ vaccineannually. Folic acid (5 mg) should be given once dailyboth preconceptually and throughout pregnancy.1

Hydroxycarbamide (hydroxyurea) should be stopped atleast 3 months before conception and angiotensin-convert-ing enzyme inhibitors and angiotensin receptor blockersbefore conception.

Sr. Consultant Obs & Gynae, Apollo Hospital, Bilaspur, India.Received: 14.6.2012; Accepted: 2.7.2012; Available online: 7.7.2012Copyright � 2012, Indraprastha Medical Corporation Ltd. All rights reserved.http://dx.doi.org/10.1016/j.apme.2012.07.002

Apollo Medicine 2012 SeptemberVolume 9, Number 3; pp. 181e183 Review Article

ANTENATAL CARE

Women with SCD should aim to avoid precipitating factorsof sickle cell crises such as exposure to extreme tempera-tures, dehydration and overexertion. Persistent vomitingcan lead to dehydration and sickle cell crisis. Womenwith HbSC experience fewer adverse outcomes, but thereis still evidence of an increased incidence of painful crisesduring pregnancy, fetal growth restriction, antepartumhospital admission and postpartum infection. Althoughoutcomes among women with HbSC are better than inwomen with HbSS, some do have serious, unpredictablecomplications, and women with HbSC should thereforebe monitored in the same way as those with HbSS.3

Management & treatment

Women should be offered a viability scan at 7e9 weeks ofgestation and the routine first-trimester scan (11e14 weeksof gestation) followed by a detailed anomaly scan at 20weeks of gestation. In addition, women should be offeredserial fetal biometry scans (growth scans) every 4 weeksfrom 24 weeks of gestation. Routine prophylactic transfu-sion is not recommended during pregnancy for womenwith SCD. If acute exchange transfusion is required forthe treatment of a sickle complication, it may be appropriateto continue the transfusion regimen for the remainder of thepregnancy. Blood should be matched for an extendedphenotype including full rhesus typing (C, D and E) aswell as Kell typing.

The influenza vaccine should be recommended if it hasnot been administered in the previous year. Iron supplemen-tation should be given only if there is laboratory evidenceof iron deficiency. Women with SCD should be consideredfor low-dose aspirin 75 mg once daily from 12 weeks ofgestation in an effort to reduce the risk of developing pre-eclampsia. Women with SCD should be advised to receiveprophylactic low-molecular-weight heparin during ante-natal hospital admissions.

Non-steroidal anti-inflammatory drugs (NSAIDs) shouldbe prescribed only between 12 and 28 weeks of gestationowing to concerns regarding adverse effects on fetal devel-opment blood pressure and urinalysis should be performedat each consultation, and midstream urine for culture per-formed monthly.4

EMERGENCY MANAGEMENT

Pregnant women presenting with acute painful crisis shouldbe rapidly assessed by the multidisciplinary team andappropriate analgesia should be administered. The

requirement for fluids and oxygen should be assessed.Thromboprophylaxis can be given to women admitted tohospital with acute painful crisis but Pethidine should beavoided because of the associated risk of seizures.

SCD is associated with other acute complicationsincluding ACS, stroke and acute anemia. After acutepain, ACS is the most common complication, reported in7e20% of pregnancies. Top-up blood transfusion may berequired if the hemoglobin is falling, and certainly if thehemoglobin is less than 6.5 g/dl, but in severe hypoxia,and if the hemoglobin level is maintained, exchange trans-fusion will be required.5,6

Acute anemia in women with SCD may be attributableto erythrovirus infection. Infection with erythrovirus inSCD causes a red cell maturation arrest and an aplasticcrisis characterized by a reticulocytopenia. Therefore,a reticulocyte count should be requested in any woman pre-senting with an acute anemia and, if low, may indicateinfection with erythrovirus. Other investigations willdepend on the clinical scenario but may include bloodcultures, chest X-ray, urine culture and liver function tests.In case of low levels of hemoglobin and erythrovirus infec-tion blood transfusion may be required. With erythrovirusinfection there is the added risk of vertical transmission tothe fetus, which can result in hydrops fetalis, hence a reviewby a fetal medicine specialist is indicated. Women withSCD can develop anemia owing to bleeding or any othercauses of anemia incidental to the SCD. Rare causes ofanemia in SCD include malaria and, occasionally, splenicsequestration in women with a mild phenotype.

LABOR CARE

Pregnant women with SCD who have a normally growingfetus should be offered elective birth through induction oflabor, or by elective caesarean section if indicated, after38þ0 weeks of gestation. SCD should not in itself beconsidered a contraindication to attempting vaginal deliveryor vaginal birth after caesarean section. Blood should becross-matched for delivery if there are atypical antibodiespresent (since this may delay the availability of blood),otherwise a ‘group and save’ will suffice. In women whohave hip replacements (because of avascular necrosis) itis important to discuss suitable positions for delivery. It isrecommended that, like most ‘high-risk’ conditions,delivery of the baby at 38e40 weeks of gestation willprevent late pregnancy complications and associatedadverse perinatal events.

Women should be kept warm and given adequate fluidduring labor. Continuous intrapartum electronic fetal heartrate monitoring is recommended owing to the increased

182 Apollo Medicine 2012 September; Vol. 9, No. 3 Sharma

risk of fetal distress which may necessitate operativedelivery. There is an increased risk of painful crisis withprotracted labor (more than 12 h), but this is oftensecondary to dehydration. In this situation, if the womanis well hydrated and labor is progressing, the labor shouldbe carefully supervised; caesarean section should be consid-ered if labor is not progressing well and delivery is notimminent. The demand for oxygen is increased during theintrapartum period and the use of pulse oximetry to detecthypoxia in the mother is appropriate during labor. Arterialblood gas analysis should be performed and oxygen therapyinstituted if oxygen saturation is 94% or less. The clinicianshould have a low threshold to commence broad-spectrumantibiotics.8,9

Postpartum contraceptive advice should be given to allof them Prostoge containing contraceptive like proges-terone only pills, cerazette injectable contraceptives(Depo-Provera) levenorgestrel intrauterine system (MirenaIUS) are safe and effective in SCD. Estrogen-containingcontraceptives should be used as second-line agents. Barriermethods are as safe and effective in women with SCD as inthe general population.

DISCUSSION

SCD is associated with both maternal and fetal complica-tions and is associated with an increased incidence of peri-natal mortality, premature labor, fetal growth restriction andacute painful crises during pregnancy. Some studiesdescribe an increase in spontaneous miscarriage, antenatalhospitalization, maternal mortality, delivery by caesareansection, infection, thromboembolic events and antepartumhemorrhage. An increased risk of pre-eclampsia and preg-nancy-induced hypertension has been described in otherstudies but not in all. In HbSC there are fewer reported

adverse outcomes, but there is evidence of an increasedincidence of painful crises during pregnancy, fetal growthrestriction, antepartum hospital admission and postpartuminfection.

CONFLICTS OF INTEREST

The author has none to declare.

REFERENCES

1. Green top guidelines. Royal College of Obstetricians andGynecologists.

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4. Disease Control Priorities in Developing Countries. 2nd ed.Washington, DC/New York, NY: The World Bank/OxfordUniversity Press; 2006: 663e80.

5. Chakravarti A, Li CC, Buetow KH. Estimation of the markergene frequency and linkage disequilibrium from conditionalmarker data. Am J Hum Genet. 1984;36:177e186.

6. Davies SC, Brozovi M. The presentation, management andprophylaxis of sickle cell disease. Blood Rev. 1989;3:29e44.

7. Serjeant GR. The emerging understanding of sickle celldisease. Br J Haematol. 2001;112:3e18.

8. Streetley A, Latinovic R, Hall K, Henthorn J. Implementationof universal newborn bloodspot screening for sickle cell diseaseand other clinically significant haemoglobinopathies inEngland: screening results for 2005e7. J Clin Pathol.2009;62:26e30.

9. Angastiniotis M, Modell B, Englezos P, Boulyjenkou V.Prevention and control of haemoglobinopathies. Bull WorldHealth Organ. 1995;73:375e386.

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