Pregnancy and Its Outcome in Sickle Cell Hemoglobinopathies: A Study of Central India
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1 Original Article Pregnancy and Its Outcome /jp-journals in Sickle Cell Hemoglobinopathies Pregnancy and Its Outcome in Sickle Cell Hemoglobinopathies: A Study of Central India 1 Ashwini Gaddikeri, 2 Sandhya P Pajai, 3 Archana D Rathod ABSTRACT Sickle cell hemoglobinopathies are the most important disorders of hemoglobin structure associated with pregnancy. The effect of pregnancy on patients with sickle cell disease and the effects of maternal sickle cell disease on the outcome of pregnancy have been the subject of many discussions. Objective: 1. To study the effect of sickle cell hemoglobinopathies over the course of pregnancy. 2. To study the complications occurring in patients of sickle cell hemoglobinopathies during antepartum, intrapartum, and postpartum period. 3. To study the effect of maternal sickle cell hemoglobinopathies on the fetus and its outcome. 4. To compare pregnancy, including maternal and fetal outcome, in sickle cell hemoglobinopathy patients with that of controls having normal HbAA pattern. Materials and methods: This study was carried out from December 15, 2010 to September 15, 2012 in the Department of Obstetrics and Gynaecology. Study design: A hospital-based prospective study, the subjects consisted of 54 pregnant women with sickle cell hemoglobinopathy, of which 12 had homozygous sickle cell disease or sickle cell anemia (HbSS) and 42 had sickle trait (HbAS); 54 pregnant women with normal Hb pattern, i.e., HbAA pattern, were chosen as control and their maternal and fetal outcome were noted and compared with that of pregnant women with normal HbAA pattern. Results: The most common complication in the present study was anemia and was seen in 85.19% of subjects and 66.67% of controls. Sickle cell anemia is a significant cause of spontaneous abortions. Thus, past pregnancy wastage was seen in 24.07% of subjects and 14.81% of control. Conclusion: Pregnancy in sickle cell hemoglobinopathies mandates vigilant multidisciplinary management so as to reduce maternal and fetal morbidity and mortality Keywords: Complications during pregnancy, Hemoglobinopathies, Pregnancy outcome, Sickle cell. 1 Senior Resident, 2 Professor and Head, 3 Associate Professor 1,2 Department of Obstetrics and Gynecology, Shri Vasantrao Naik Government Medical College, Yavatmal, Maharashtra, India 3 Department of Obstetrics and Gynecology, Government Cancer Hospital, Aurangabad, Maharashtra, India Corresponding Author: Archana D Rathod, Associate Professor, Department of Obstetrics and Gynecology Government Cancer Hospital, Aurangabad, Maharashtra, India Phone: , archanarathod7@gmail.com How to cite this article: Gaddikeri A, Pajai SP, Rathod AD. Pregnancy and Its Outcome in Sickle Cell Hemoglobinopathies: A Study of Central India. J South Asian Feder Obst Gynae 2017;9(4): Source of support: Nil Conflict of interest: None Date of received: 10 November 2017 Date of acceptance: 20 December 2017 Date of publication: April 2018 INTRODUCTION Pregnancy is a blessing to every woman, a sign of womanhood. But it may be a burden to the life in many women, and causes are innumerable. One such cause is sickle cell hemoglobinopathies, which pose a threat to the lives of both the pregnant woman and her baby. Sickle cell disorders account for about 70% of the worldwide hemoglobin disorders. 1,2 As per the World Health Organization (WHO) report, 3 60 million carriers of sickle cell and 1,20,000 sickle cell homozygotes are added every year in the world. Inherited in an autosomal recessive manner, it is characterized primarily by chronic anemia and periodic episodes of pain. During pregnancy, patients with major sickle hemoglobinopathies are susceptible to exacerbations of their disease, probably as a result of increased metabolic demands, hypercoagulable state, and increased vascular stasis. Vasoocclusive crisis is more common in the later half of pregnancy. There is an increased incidence of pyelonephritis, pulmonary infarction, pneumonia, acute chest syndrome, prematurity of infants, low birth weight, and fetal death in pregnant women having sickle cell anemia. The birth weight of infants is below average and fetal wastage is high, the cause of which is obscure, but may sometimes result from vasoocclusion of placenta. The maternal mortality in sickle cell disease was formerly prohibitively high, rates averaging 33%, but is now much lower. 4 India With a population of 1,000 million at the new millennium (2000) year and a birth rate of 25 per 1,000 live Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):
2 Ashwini Gaddikeri et al births, there would be about 45 million carriers and about 15,000 infants born each year with hemoglobinopathies in India. However, the exact share of sickle cell disease is still unknown in India. The sickle cell hemoglobinopathy has remained a neglected field of research in India and the magnitude of the problem has never been properly appreciated. 1 Considering the above said facts, the following study was undertaken to know the course of pregnancy in patients with sickle cell hemoglobopathies, and its effect on maternal and fetal outcome. MATERIALS AND METHODS This study was carried out from December 15, 2010 to September 15, 2012 in the Department of Obstetrics and Gynaecology of Shri Vasantrao Naik Government Medical College of Yavatmal. Study Design A hospital-based prospective study, where pregnant women having sickle cell hemoglobinopathies were studied and their maternal and fetal outcome were noted and compared with that of pregnant women with normal HbAA pattern. Study Setting This study was conducted in the Department of Obstetrics and Gynaecology at a government medical college of Central India. Study Duration The study was carried out from December 15, 2010 to September 15, 2012, total duration of the study being 21 months. Data collection was done from December 15, 2010 to June 15, Data entry and data analysis were done from June 16, 2012 to September 15, Sampling The study population consisted of pregnant women attending antenatal outpatient department (OPD) services or admitted in the antenatal wards in the Department of Obstetrics and Gynaecology during the period from December 15, 2010 to June 15, Sample Size The total number of pregnant women studied during the study period was 108, of whom 54 women had sickle cell hemoglobinopathies (12 had homozygous sickle cell disease of HbSS and 42 had sickle cell trait of HbAS), taken as study subject and remaining 54 women had normal hemoglobin HbAA pattern, taken as controls. Selection Criteria Inclusion Criteria Pregnant women attending antenatal OPD having sickle cell hemoglobinopathies as diagnosed by Hb electrophoresis, who were willing to participate in the study. Pregnant women having sickle cell hemoglobinopathies, as diagnosed by Hb electrophoresis, who were admitted in ward and were willing to participate in the study. Exclusion Criteria Women not willing to participate in the study or not providing written informed consent. Pregnancies which terminated in abortion in the study were excluded. Data Analysis All cases and controls were followed through pregnancy, labor, and puerperium. The statistical difference of complications between the two groups of patients was calculated by Fisher extract test; p value <0.05 was considered significant. RESULTS The study subjects consisted of 54 pregnant women with sickle cell hemoglobinopathy. Of them 12 had homozygous sickle cell disease or sickle cell anemia (HbSS) and 42 had sickle trait (HbAS); 54 pregnant women with normal Hb pattern, i.e. HbAA pattern, were chosen as control (Table 1). Table 2 shows that previous spontaneous abortions were seen in 14.81% of subjects and 9.26% of controls; 400 Severe anemia, Hb <7 gm% Table 1: Distribution of subjects and controls depending on the severity of anemia Moderate anemia, Hb gm% Mild anemia, Hb 10 <11 gm% No anemia (WHO) Hb>11 gm% 5 No anemia (developing countries) Hb> 10 gm% 5 Group No. % No. % No. % No. % No. % SS (n = 12) AS (n = 42) AA (n = 54)
3 Pregnancy and Its Outcome in Sickle Cell Hemoglobinopathies Table 2: Maternal complications during pregnancy, labor, and puerperium SS (n = 12) AS (n = 42) Maternal complications AA (n = 54) % % Statistical significance* % Statistical significance* Anemia Significant (p = ) Not significant (p = ) UTI Significant (p = ) 26.2 Not significant (p = ) HDP Not significant (p = ) Not significant (p = ) Jaundice 0 25 Significant (p = ) 2.38 Not significant (p = ) Crisis Significant (p = ) 0 Postpartum hemorrhage Not significant (p = ) 7.14 Not significant (p = ) Puerperal complications Significant (p = ) 2.38 Not significant (p = ) Maternal mortality Not significant (p = ) 0 *Calculated by Fisher s exact test; p < 0.05 is taken as significant value. Calculated in comparison to AA controls; HDP: Hypertensive disorders of pregnancy; UTI: Urinary tract infections 33.33% patients in SS group (p = ) and 9.52% patients in AS group (p = ) had spontaneous abortions in the previous pregnancies. Thus, previous spontaneous abortions were statistically significant (p < 0.05) in SS group. When compared with controls, it was not significant in AS group (Table 3). Previous perinatal loss was seen in 9.26% of subjects and 5.56% of controls; 6.67 % patients in SS group (p = ) and 7.14% patients in AS group (p = ) had perinatal loss in previous pregnancies. Thus, previous perinatal loss was not statistically significant in either SS or AS patients (p > 0.05) when compared with controls (Table 4). Thus, past pregnancy wastage was seen in 24.07% of subjects and 14.81% of controls. Past pregnancy wastage in SS group was 50% (p = ) and in AS group it was 16.67% (p = ). Thus, past pregnancy wastage was statistically significant in SS group (p < 0.05) when compared with controls, but it was not significant in AS group (Table 3). In subjects, average Hb% in SS group was ± 1.0 gm% and in AS group was 8.72 ± gm%. Average Hb% in controls (AA) was 9.29 ± gm%. The prevalence of anemia (Hb < 10 gm%)16 was: In SS group 100 % (p = ) Table 3: Past pregnancy wastage in subjects and controls Previous spontaneous abortions Previous perinatal loss Group No. % No. % SS AS AA In AS group 80.95% (p = ) In AA group % Thus, anemia (Hb < 10 gm%) was statistically significant in SS patients (p < 0.05) when compared with controls, but was not significant in AS patients. Severe anaemia (Hb < 7 gm%) was seen in 33.33% of SS patients (p = ), 7.14% of AS patients (p = ), and 1.85% of controls. Thus, severe anemia was statistically significant in SS patients (p < 0.05) when compared with controls. Blood transfusion was given at some stage in the study to 100% of SS patients (p = ), 38.09% of AS patients (p = ), and 16.67% of controls. Thus, blood transfusion was statistically significant in both SS and AS patients (p < 0.05) when compared with controls. DISCUSSION Mean Hb% in controls (AA) was ± gm%. The mean Hb% in subjects was ± gm%, gm% less than that of controls. Among the subjects, mean Hb% in SS group was ± 1.0 gm% and in AS group, ± gm%. Anemia (Table 1) was seen in 85.19% of subjects and 66.67% of controls. Anemia was significant in SS patients compared with controls (100 vs 66.67%, p = ). Severe anemia was also significant in SS patients when compared with controls (33.33 vs 1.85%, p = ). In sickle cell anemia (HbSS) patients, incidence of anemia was reported to be 93% by Hendrickse et al, 6 65% by Tuck et al, % by Omo-Aghoja and Okonofua, 8 and 84.3% (p < ) by Al Jama et al. 9 Table 4: Summary of pregnancy outcome in subjects and controls SS AS Pregnancy outcome AA % Statistical significance* % Statistical significance* Previous spontaneous abortions Significant (p = ) 9.52 Not significant (p = ) Previous pregnancy wastage Significant (p = ) Not significant (p = ) Preterm deliveries Not significant (p = ) 9.52 Not significant (p = ) Cesarean sections Not significant (p = ) Not significant (p = ) *Calculated by Fisher s exact test; p < 0.05 is taken as significant value. Calculated in comparison with AA controls Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):
4 Ashwini Gaddikeri et al Table 5: Distribution of birth weights in subjects and controls <1,000 gm 1,000 1,500 gm 1,500 2,000 gm 2,000 2,500 gm 2,500 gm Group No. % No. % No. % No. % No. % SS (n = 13) AS (n = 44) AA (n = 55) Table 6: Summary of fetal complications and perinatal outcome Fetal complications and SS AS perinatal outcome AA% % Statistical significance* % Statistical significance* Low birth weight Significant (p = ) Not significant (p = ) IUGR Significant (p = ) Not significant (p = ) Still births Not significant (p = ) 2.38 Not significant (p = ) END Not significant (p = ) 7.14 Not significant (p = ) Perinatal mortality 55.56/1, /1,000 Not significant (p = ) 95.24/1,000 Not significant (p = ) END: Early neonatal death; IUGR: Intrauterine growth retardation; *Calculated by fisher s exact test; p < 0.05 is taken as significant value; Calculated in comparison to AA control About 80.95% of AS patients had anemia. It was not statistically significant (p = ) when compared with controls. Among the other complications (Table 2), urinary tract infections (UTIs) were significant in SS patients when compared with controls (41.67 vs 11.11%, p = ). The UTI during pregnancy in sickle cell anemia is noted to be 33% by Freeman and Ruth, % by Rahimy Mohamed et al, % by Rathod et al, % (p < ) by Al Jama et al. 9 Jaundice was seen in 25% of SS patients (p = when compared with AS patients and p = when compared with controls) and 2.38% of AS patients (p = ) had jaundice. Jaundice was not seen in any of the control subjects. Thus, jaundice was a statistically significant complication in SS patients (p < 0.05) when compared with AS patients and controls. Crisis was significant in SS patients when compared with AS patients (58.33 vs 0%, p < 0.05). About 33.33% patients had painful crisis and 25% had hemolytic crisis. Crisis in SS patients was noted to be 48.6% by Dare et al, 13 56% by El-Shafei et al, 14 and 40% by Sonwane and Zodpey. 15 Painful crisis was reported to be 50% by Seoud et al, 16 57% by Rahimy Mohamed et al, % by Odum et al, % by Omo Aghoja and Okonofua, % by Al Jama et al. 9 Hemolytic crisis was 34.4% by Odum et al 17 and 17.7% by Al Jama et al. 9 There was one maternal death in SS group, on the 7th day of postcesarean section (indicated for prolonged second stage of labur), due to pneumococcal pneumonia and septicemia. As seen in Tables 3 and 4, past pregnancy wastage was significant in SS group when compared with control group (50 vs 14.81%, p = ). Previous spontaneous abortions were also significant in SS patients (33.33 vs 9.26%, p = ). Freeman and Ruth 10 reported pregnancy wastage of 36.4% in SS patients in their study. In the study by Rahimy Mohamed et al, 11 previous unsuccessful pregnancies were reported to be 21.43% in SS patients. Table 5 shows the distribution of birth weight of infants. The mean birth weight of infants born to SS mothers was ± gm, that of AS mothers was ± gm, and of those born to controls was ± gm. When compared with the control group, there was significantly higher risk of adverse fetal outcome in the SS group. As shown in Table 6, low birth weight of infants was statistically significant in SS group compared with controls (84.62 vs 23.64%, p = ; Table 6). One infant in SS group had extremely low birth weight (<1,000 gm). Low birth weight reported by different studies are 31% by Poddar et al, 18 42% by Serjeant et al, % by Sonwane and Zodpey. 15 In studies by Kale et al 20 (56%, p < 0.05) and Al Jama et al 9 (16.5% p < 0.05), low birth weight in SS group was significant. In AS subjects, 36.36% infants had low birth weight, which, though higher than in controls, was not significant (p = ). Intrauterine growth retardation was statistically very significant (p < 0.01) in SS patients compared with controls (50 vs 11.11%, p = ). Al Jama et al 9 reported 20.8% intrauterine growth retardation (IUGR) in SS patients, which was statistically significant (p < ) when compared with controls in their study. The significant antenatal complications seen in SS subjects in the study were anemia, UTI, sickling crisis, and jaundice. In AS subjects, though the complications were high, they were not significant. Anemia was the most common complication, with most of the patients having either moderate or severe anemia. In SS group, anemia was seen in all the patients and was either of moderate 402
5 Pregnancy and Its Outcome in Sickle Cell Hemoglobinopathies Table 7: Labor and mode of delivery in subjects and controls Preterm delivery Full-term normal delivery Cesarean section Group No. % No. % No. % SS (n = 12) AS (n = 42) AA (n = 54) *Calculated by Fisher s exact test; p < 0.05 is taken as significant value. Calculated in comparison to AA controls or of severe grades. Puerperal complications were also significantly high in SS patients than AA and AS patients. Maternal mortality was not significant in either group. Past pregnancy wastage and spontaneous abortions were also significant in SS subjects. Among the fetal complications, low birth weight and IUGR were significant in SS group. Though the rate of preterm deliveries in SS mothers was more than in AA mothers, it was not significantly high. In AS patients, preterm delivery rate was similar to that of women having normal HbAA (Table 7). Perinatal loss in SS group was more than that of AS and AA groups, but was not statistically significant. CONCLUSION Thus, sickle cell hemoglobinopathies put pregnant woman and her fetus into several complications, and the pregnancy outcome may not be fruitful always. Women with sickle cell trait have a near-normal pregnancy with a good maternal and fetal outcome, almost comparable to that of women with normal HbAA pattern. But, in sickle cell anemia patients, pregnancy is a burden which puts the woman into a high-risk group with high rates of antenatal and postnatal complications. The course of pregnancy and its outcome is also gloomy, with high rates of pregnancy wastage and preterm deliveries. The fetus of a sickle cell anemia mother also suffers the brunt of the disease by having higher rates of low birth weight and IUGR. So pregnancy in sickle cell hemoglobinopathies mandates vigilant multidisciplinary management, so as to reduce maternal and fetal morbidity and mortality. REFERENCES 1. Balgir R. Epidemiology, population health genetics and phenotypic diversity of sickle cell disease in India. Int J Biol Anthropol 2007;1(2). 2. Angastiniotis M, Modell B, Englezos P, Boulyzhenkov V. Prevention and control of hemoglobinopathies. Bull World Health Organ 1995;73(3): WHO Report. Community control of hereditary anemias. Memorandum from a WHO meeting. Bull World Health Organ 1983;61(1): Beutler E. The sickle cell diseases and related disorders. In: Ernest B, et al., editors. Williams hematology. 5th ed. New York, NY: McGraw-Hill; Grewal A. Anaemia and pregnancy: anaesthetic implications. Indian J Anaesth 2010;54: Hendrickse JP, Watson-Williams EJ, Luzzatto L, Ajabor LN. Pregnancy in homozygous sickle-cell anaemia. J Obstet Gynaecol Br Commonw 1972 May;79(5): Tuck SM, Studd J, White JM. Pregnancy in sickle cell disease in the UK. Br J Obstet Gynaecol 1983 Feb;90(2): Omo-Aghoja IO, Okonofua FE. Pregnancy outcome in women with sickle cell a five year review. Niger Postgrad Med J 2007 Jun;14(2): Al Jama FE, Gasem T, Burshaid S, Rahman J, Al Suleiman SA, Rahman MS. Pregnancy outcome in patients with homozygous sickle cell disease in a university hospital, Eastern Saudi Arabia. Arch Gynecol Obstet 2009 Nov;280(5): Freeman MG, Ruth GJ. SS disease, SC disease and CC disease: obstetric considerations and treatments. Clin Obstet Gynecol 1969 Mar;12(1): Rahimy Mohamed C, Gangbo A, Adjou R, Deguenon C, Goussanou S, Alihonou E. Effect of active prenatal management on pregnancy outcome in sickle cell disease in an African setting. Blood 2000 Sep;96(5): Rathod KB, Jaiswal KN, Shrivastava AC, Shrikhande AV. Study of placenta in sickle cell disorders. Indian J Pathol Microbiol 2007 Oct;50(4): Dare FO, Makinde OO, Faasuba OB. The obstetric performance of sickle cell disease patients and homozygous hemoglobin C disease patients in Ile-Ife, Nigeria. Int J Gynaecol Obstet 1992 Mar;37(3): El-Shafei AM, Kaur Dhaliwal J, Kaur Sandhu A, Rashid Al- Sharqi M. Indications for blood transfusion in pregnancy with sickle cell disease. Aust N Z J Obstet Gynaecol 1995 Nov;35(4): Sonwane AS, Zodpey SP. Pregnancy outcome in women with sickle cell disease/trait. J Obstet Gynecol India 2005 Sept/ Oct;55(5): Seoud MA, Cantwell C, Nobles G, Levy DL. Outcome of pregnancies complicated by sickle cell and sickle-c hemoglobinopathies. Am J Perinatol 1994 May;11(3): Odum CU, Anorlu RI, Dim SI, Oyekan TO. Pregnancy outcome in HbSS-sickle cell disease in Lagos, Nigeria. West Afr J Med 2002 Jan-Mar;21(1): Poddar D, Maude GH, Plant MJ, Scorer H, Serjeant GR. Pregnancy in Jamaican women with homozygous sickle cell disease. Fetal and maternal outcome. Br J Obstet Gynaecol 1986 Jul;93(7): Serjeant GR, Loy LL, Crowther M, Hambleton IR, Thame M. Outcome of pregnancy in homozygous sickle cell disease. Am Coll Obstet Gynecol 2004 Jun;103(6): Kale A, Panigrahi R, Sethi P. Perinatal outcome in pregnancy with sickle cell anemia. J Obstet Gynecol India 2008 Nov/ Dec;58(69): Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):
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