|Year : 2017 | Volume
| Issue : 4 | Page : 242-246
Sickle cell disease complicating pregnancy: A retrospective study
B Kavitha, Basanta H Hota
Department of Obstetrics and Gynaecology, Mamata Medical College, Khammam, Telangana, India
|Date of Web Publication||26-Dec-2017|
Dr. B Kavitha
Department of Obstetrics and Gynaecology, Mamata Medical College, Khammam - 507 002, Telangana
Source of Support: None, Conflict of Interest: None
Introduction: Sickle cell disease is an uncommon cause of anemia and jaundice during pregnancy. Sickle cell crisis may lead to several maternal and fetal complications.
Aims: To study maternal and fetal complications in pregnant patients with sickle cell disease.
Settings and Design: Retrospective study was carried out from case records at Mamata Medical College over a period of five years from July 2011 to June 2016.
Patients and Methods: Among 17 pregnancies in 12 cases, we studied the baseline characteristics of study population, frequency of sickle hemoglobin variants, and complications to mother and baby.
Statistical Analysis Used: Compiled data was analyzed by simple descriptive statistics and frequency tables.
Results: Most cases were primigravida (58.3%). Most common presenting features were anemia and jaundice (hemolytic crisis, 70.58%) and bone and joint pains (painful crises, 41.17%). Acute chest syndrome was seen in 5.88% of the patients. Pregnancies were complicated by severe anemia (Hb <7 gm%) in 29.41% of patients, by jaundice - 76.47%, urinary tract infection - 47.05%, pre-eclampsia - 11.76%, and hepatosplenomegaly - 17.64%. Fetal/neonatal complications were intra-uterine growth restriction (IUGR, 35.29%), perinatal death (17.64%), preterm delivery (35.3%), fetal distress (41.17%), meconium stained liquor (29.41%), meconium aspiration syndrome (11.76%), and low birth weight (58.82%). Sickling test was positive in all cases. Hemoglobin electrophoresis showed HbS. HbSS was the commonest form of sickle cell disease.
Discussion: Because of hematological changes, extra demands, and sickle crisis, complications to both mother and fetus are more common in sickle cell anemia during pregnancy than in non-pregnant state.
Conclusions: Although sickle cell anemia during pregnancy is usually associated with complications, prompt recognition and careful management reduces morbidity and mortality associated with them.
Keywords: Crisis, jaundice, sickle cell anemia
|How to cite this article:|
Kavitha B, Hota BH. Sickle cell disease complicating pregnancy: A retrospective study. J NTR Univ Health Sci 2017;6:242-6
| Introduction|| |
Sickle cell disease (SCD) is a group of inherited single-gene autosomal recessive disorders caused by 'sickle' gene, which affects hemoglobin structure (Hb S). This abnormal hemoglobin polymerises under hypoxic conditions, to form rigid and fragile, sickle-shaped red cells leading to hemolysis and vasoocclusion in microvasculature. Hb S occurs commonly in populations previously exposed to falciparum malaria, i.e., Africa, India, and Saudi Arabia. In India, in the tribal belts of Madhya Pradesh, Chhattisgarh, Odisha, and Andhra Pradesh, (especially Bhadrachalam), SCD occurs commonly and our centre receives many referrals from there. Pregnancies in women with sickle cell anemia and its complications were studied.
| Patients and Methods|| |
A retrospective study from case records, of 17 pregnancies in 12 women over a period of 5 years from July 2011–June 2016 was done. Five women delivered for second time in the study population in this hospital during the study period. Maternal hemoglobin electrophoresis was done in all cases. Antenatal, intranatal, and postnatal management was carried out as per the requirement of individual pregnancy and new born. Baseline characteristics of study population, frequency of sickle hemoglobin variants, and complications to mother and baby (fetus/newborn) were studied. Individual complication and management including blood transfusion was noted for analysis. Outcome of each pregnancy in detail was recorded. Compiled data was analyzed by simple descriptive statistics and frequency tables. As some of the patients refused for investigation of newborn for SCD, cases could not be taken for study of inheritance.
| Results|| |
Seventeen pregnancies in 12 women over a period of 5 years from July 2011–June 2016 were studied. Out of the 12 women, 5 women delivered for the second time in this hospital during the study period. Baseline characteristics of study population (N = 17) are shown in [Table 1]. Age of study population ranged from 22–30 years with mean being 25.83 years. Most of the women studied were primigravida (58.3%).
[Table 2] shows the frequency of variants of SCD in study population. This was determined on basis of percentage of Hb variants on hemoglobin electrophoresis. Presence of HbS and HbF, but no HbA is interpreted as sickle cell anemia (HbSS). Presence of HbS, but with a higher proportion of HbA than HbS is interpreted as sickle cell trait (HbAS) or sickle α-thalassemia. When overall proportion of HbS is higher than HbA and HbF, sickle beta-thalassemia is most likely. When HbA2 >3.5%, thalassemia minor is diagnosed. Presence of HbS and HbC is HbSC disease.
In the present study, out of 12 women, 6 (35.29%) had HbSS and one (5.88%) had HbSS with J-variant. HbS with β-thalassemia (HbSB) was present in five (29.41%) women. Two out of five had thalassemia minor. There were no cases of sickle cell trait and HbSC.
As shown in [Table 3], complications were calculated per 17 pregnancies. Episodes of crises: Hemolytic -12 (70.58%) and painful- 7 (41.17%) were common during pregnancy. There were no cases of aplastic crisis. Acute chest syndrome was seen in one (5.88%). Pregnancies were complicated by severe anemia <7g% in five (29.41%), jaundice - 13 (76.47%), urinary infection - 8 (47.05%), pre-eclampsia – two (11.76%), malaria - two (11.76%), and hepatosplenomegaly - three (17.64%). Two women (11.76%) had undergone splenectomy and cholecystectomy each previously, prior to pregnancy. Eleven pregnancies (64.7%) were delivered by caesarean section.
Fetal/neonatal complications as shown in [Table 4] were intra-uterine growth restriction (IUGR) - 6 (35.29%), perinatal death - three (17.64%), preterm delivery - 6 (35.29%), fetal distress - 7 (41.17%), meconium stained liquor - five (29.41%), meconium aspiration syndrome - two (11.76%), and low birth weight - 10 (58.82%).
| Discussion|| |
SCD is a group of inherited single-gene autosomal recessive disorders caused by 'sickle' gene, which affects hemoglobin structure. Hemoglobin S (Hb S) has a substitution of valine for glutamic acid in sixth position of Beta globin chain. Hb S occurs in high frequency in populations previously exposed to falciparum malaria, i.e., Africa, India, Mediterranean area, and Saudi Arabia.
The term SCD includes sickle cell anemia (HbSS) and heterozygous conditions of hemoglobin S and clinically abnormal hemoglobins. These include combination with hemoglobin C (HbSC), beta thalassemia (HbSB thalassemia), and hemoglobin D, E, or O-Arab. Hemoglobin S combined with normal hemoglobin (A), known as sickle trait (AS), is asymptomatic, except for increased risk of urinary tract infections, and microscopic hematuria.
Pathophysiology of SCD is a consequence of polymerization of the abnormal hemoglobin in low-oxygen conditions, leading to formation of rigid and fragile sickle-shaped red cells. These cells are prone to hemolysis and cause vaso-occlusion in small blood vessels, leading to acute painful crises. During pregnancy, labor and puerperium they are more frequent, severe and prolonged [20–50%]. Other morbidities like pre-eclampsia, cerebrovascular accidents, thrombo-embolism, pyelonephritis, infections, leg-ulcers are also common. Fetal complications include abortions, IUGR, stillbirths, increased perinatal mortality.
During pregnancy, SCD poses problems to both mother and fetus.[1–3] Increased maternal morbidity is due to increased episodes of vaso-occlusive crisis, acute chest syndrome and from pregnancy-related complications (RCOG guideline-61). According to Villers et al., maternal morbidity was increased due to increased rates of caesarean section, pregnancy-related events like pre-eclampsia, abruption and pulmonary complications, hypertension, and infection. However, rates of maternal morbidity from SCD were same during pregnancy as non-pregnant state in a study by Smith et al.
Hemoglobin electrophoresis showed HbS in all women confirming the diagnosis of SCD. A total of 35.29% cases were homozygous in comparison to 70.5% in Brazilian study. In heterozygous condition, complications are less severe.
Most cases (58.3%) were primigravida in present study. Most common complications were crises presenting with anemia, jaundice, and joint pains. Around 29.41% had severe anemia. In normal, iron-replete women, RBC mass increases by 400–450 mL during pregnancy. This increase is not achievable in SCD. Intravascular hemolysis still reduces the RBC count, hence anemia is invariable. A total of 70.58% had episodes of hemolytic crisis during pregnancy. All women in the present study received blood transfusions during pregnancy. According to a study by Ngo et al., despite prophylactic blood transfusions, SCD remains a complicating factor in pregnancy. Painful crisis is the most frequent complication of SCD during pregnancy according to RCOG  [25–50%]. It complicated 41.17% of all pregnancies in the present study. In a study by Leborgne et al., vaso-occlusive crisis was responsible for 88% of antenatal admissions.
Out of 13 pregnancies with jaundice (76.47%), two had severe jaundice with serum bilirubin more than 10 mg/dl. Four had bilirubin between 5–10 mg/dl, and 7 had mild jaundice with bilirubin less than 5 mg/dl. The cause of jaundice was hemolysis as evidenced by raised serum levels of indirect bilirubin and lactate dehydrogenase.
Only one patient (5.88%) presented with acute chest syndrome. Maternal mortality (2–7%) is caused by acute chest syndrome, pulmonary thrombo-embolism, pulmonary hypertension, cardiomyopathy, or renal failure. There was no maternal mortality in present study similar to a study by Sun et al. They concluded that those caring for women with SCD should be aware of increased risk for pregnancy complications, although overall pregnancy outcome is favourable.
Pre-eclampsia was present in 11.76% of pregnancies in present study, similar to 10.6% in a report by Al Jama et al. Perhaps because of underlying renal disease, hypertension, placental ischemia or endothelial damage, pre-eclampsia is more likely., In studies by Afolabj et al. and Serjeant, there was no increase in pre-eclampsia in SCD.
A total of 47.05% pregnancies were complicated by urinary tract infection in present study in contrast to a study by Afolabj et al., where there was no significant difference between SCD and normal women.
Most common organism isolated in UTI (47.05%) was E. Coli (five), followed by Klebsiella (three). Five pregnancies were complicated by symptomatic infection with fever associated with chills and burning micturition. Three were asymptomatic. None of them developed pyelonephritis.
In the present study, 11.76% pregnancies were affected by falciparum malaria and 17.64% had hepato-splenomegaly. Falciparum malaria was a major cause of maternal morbidity in SCD, as per a study by Rahimy et al.
Rate of caesarean delivery was higher (64.7%) in the present study similar to a study by Barfield et al., who concluded that SCD was positively associated with caesarean delivery and inductions. Although SCD per se is not an indication for caesarean delivery, it is associated with complications like pre-eclampsia, IUGR, fetal distress, and meconium stained liquor, which warrant LSCS (Lower segment caesarean section). Indications for caesarean section (11 cases) in present study were fetal distress with abnormal cardiotocogram (CTG) and/or meconium stained liquor (7), previous LSCS (three), and persistent brow presentation (one). There was only one preterm LSCS for severe uteroplacental insufficiency with reversal of flow in diastole.
Out of 17 pregnancies, 14 were allowed vaginal delivery, remaining three being elective LSCS for prior caesarean. Eight of them underwent emergency LSCS. Intrapartum, 7 pregnancies (41.17%) had fetal distress and abnormal CTG, five (29.4%) deliveries were complicated by meconium stained liquor. One had persistent brow presentation. Abnormal CTG patterns seen were sinusoidal pattern, fetal bradycardia, and persistent late decelerations with absent variability. Intra-operatively, one primigravida with 40 weeks 4 days gestational age with sinusoidal pattern on CTG had postpartum hemorrhage due to adherent placenta.
Fetal concerns in SCD are consequences of utero-placental insufficiency, alloimmunization, and opioid exposure. Several studies have documented increased risk of IUGR, preterm delivery, and stillbirth., In the present study, 35.29% had oligohydramnios and/or IUGR, while only 21% had IUGR in a study by Smith et al. Pre-eclampsia and severe anemia (crisis), resulting in placental ischemia were identified as risk factors for IUGR.
Fetal distress with abnormal fetal heart rate pattern was seen in 41.17%. Abnormal CTG patterns seen were sinusoidal pattern, fetal bradycardia, and late decelerations. A total of 29.41% had meconium stained liquor, but only 11.76% developed meconium aspiration syndrome.
There were 17.64% perinatal deaths in present study and 66% of these were intrauterine death in contrast to a study by Al Jama et al., where perinatal mortality was only 7.8% and 63% of these were still births. However, 99% of those pregnancies carried to delivery resulted in live birth in a study by Smith et al. In a study by Leborgne et al., IUGR and IUD were most frequent fetal complications similar to the present study. Incidence of perinatal mortality was similar to the present study in a study by Afolabi et al. (18.7%).
Most of the deliveries in the present study occurred at term gestation, only 35.29% being preterm. Five delivered vaginally - two IUD and three IUGR (two had pre-eclampsia). There was only one preterm LSCS for severe uteroplacental insufficiency with reversal of flow in diastole. In a study by Al Jama et al., rate of preterm deliveries was only 12.6%. However, preterm deliveries were more common in homozygous SCD with significant P < 0.01 when compared to controls in study by Serjeant et al. In a study by Sun, there was increased risk of IUGR and preterm birth in SCD when compared to women with normal hemoglobin.
Birth weight was ≤2.5 Kg in 58.82% because of IUGR and preterm births similar to a study by Serjeant et al., where it was significantly affected by sickle-related events. All other studies ,,, have also documented increased low birth weights similar to present study.
Treatment of SCD in pregnancy includes adequate folic acid for active erythropoiesis – 4 mg/day. Iron supplementation should not be given unless documented iron deficiency is present. No routine prophylactic blood transfusions are advocated by RCOG. Only indicated blood transfusions are given for episodes of hemolytic, bony crisis, aplastic crisis [Hb A1 <20%; hematocrit <25] or infection.
Episodes of crisis are managed by intravenous hydration, pain relief with morphine, demerol, fentanyl [patient controlled pump], partial exchange of leucocyte-poor RBC transfusion, broad-spectrum antibiotic [as infection is a frequent trigger], nasal oxygen, and bronchodilators.
| Conclusion|| |
SCD during pregnancy is definitely associated with significant morbidity and occasional mortality in both mother and baby, which can be reduced by prompt recognition of complications and their careful management. Premarital counselling of parents and the patient regarding the disease, its effect on pregnancy, and effect to the offspring if either/both parents are affected must be explained well to reduce the SCD population and avoid unnecessary burden to person and the country.
We are thankful to our head of the department for permitting us to carry out the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]