International Journal of Gynecology and Obstetrics 119 (2012) 224–226

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International Journal of Gynecology and Obstetrics

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CLINICAL ARTICLE

Morbidity and pregnancy outcomes associated with sickle cell anemia amongSaudi women

Maryam A. Al Kahtani a,⁎, Mohammad AlQahtani b, Mashael M. Alshebaily a, Mohamed Abd Elzaher a,Ashraf Moawad c, Naji AlJohani b

a Department of Obstetrics and Gynecology, King Khalid University Hospital, Riyadh, Saudi Arabiab College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabiac Department of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia

⁎ Corresponding author at: Department of ObstetricsUniversity Hospital, 11411 Riyadh, Saudi Arabia. Tel.:14679557.

E-mail address: dr_maryama@yahoo.com (M.A. Al K

0020-7292/$ – see front matter © 2012 International Fedhttp://dx.doi.org/10.1016/j.ijgo.2012.07.008

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 15 March 2012Received in revised form 7 July 2012Accepted 21 August 2012

Keywords:MorbidityMortalityPregnancySaudi ArabiaSickle cell crisisSickle cell disease

Objective: To identify morbidity and pregnancy outcomes associated with sickle cell disease (SCD) amongpregnant Saudi women. Methods: A 10-year retrospective study was conducted at King Khalid UniversityHospital in Riyadh, Saudi Arabia, that included 392 cases of SCD in pregnancy and 784 controls with normalhemoglobin phenotype, who were selected and matched for age, parity, and delivery outcome. The main out-come measures were morbidity, maternal outcomes, and fetal outcomes. Results: The incidence of SCD was1.1% among all deliveries, with 2 maternal deaths (0.5%) and a perinatal mortality rate of 77.7 per 1000 de-liveries. The major maternal complications in the SCD group were anemia (86.2%); sickle cell crisis (64.8%overall, with 43.1% vaso-occlusive, 21.2% hemolytic, and 0.5% sequestration or aplastic); bacterial infection(8.8%); preterm delivery (15.3%); and pre-eclampsia (9.7%). Fetal growth restriction and stillbirths accountedfor 65.6% of the perinatal mortality. Blood transfusion was indicated in 33.7% of pregnancies in the SCD group.Conclusion: Pregnant Saudi women with SCD are at increased risk for pregnancy-related complications, as

well as fetal morbidity and mortality. A critical need exists among Saudi hospitals for a multidisciplinaryapproach to the management of pregnancies complicated by SCD.© 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Sickle cell disease (SCD), which affects 1 in 600 African Americans,is the most frequent hemoglobinopathy reported in the USA [1]. Preg-nant women with SCD experience an increased incidence of medicaland pregnancy-related complications [2]. Nonetheless, medical ad-vances in obstetrics and neonatology have encouraged women withSCD to attempt pregnancy [2–4]. In the USA, mortality rates amongpregnant women with SCD have been falling consistently since the1970s [5].

Most studies of SCD in pregnancy document neonatal risks, in-cluding premature delivery and intrauterine growth restriction(IUGR); however, there is little available information with regardsto maternal outcomes [6,7]. While any pregnancy can carry the riskof multiple complications, such as pregnancy-induced hypertension,pre-eclampsia, and pyelonephritis, most studies fail to demonstratean increased risk of pre-eclampsia or eclampsia among pregnantwomen with SCD [6–8]. Most deaths among pregnant women withSCD are attributed to thromboembolic events [2].

and Gynecology, King Khalid+966 554545828; fax: +966

ahtani).

eration of Gynecology and Obstetrics.

Given the lack of information currently available on maternal out-comes, the aim of the present study was to evaluate morbidity andpregnancy outcomes among Saudi women with SCD.

2. Materials and methods

A retrospective study was conducted at King Khalid UniversityHospital (KKUH), which is affiliated to King Saud University inRiyadh, Saudi Arabia. Ethics approval was obtained from the Collegeof Medicine Research Center, KKUH. Informed patient consent formswere also secured.

Data were compiled retrospectively on all pregnant Saudi womenwith homozygous SCD who received treatment in the Departmentof Obstetrics and Gynecology, KKUH, between August 1, 2001, andDecember 15, 2010. Women with twin pregnancies, hemoglobin S/βthalassemia, or hemoglobin C (SC) thalassemia were excluded. TheSCD group comprised 392 women who met the inclusion criteria. Acontrol group of 784 Saudi women with normal hemoglobin pheno-type, selected and matched for age, parity, and delivery outcome,was also included in the analysis.

Characteristics assessed included age; parity; information aboutdelivery (gestational age and mode); information about the infant(birth weight, birth weight percentile, Apgar score at 5 and 7 mi-nutes); frequency of prenatal visits; gestational age at first prenatal

Published by Elsevier Ireland Ltd. All rights reserved.

Table 2Fetal outcomes in the sickle cell disease and control groups.a

Outcome SCD group (n=392) Control group (n=784) P valueb

Live births 373 (95.2) 778 (99.2) b0.001Mean birth weight, g 2850±540 3456±496 b0.0001Low birth weight 73 (18.6) 71 (9.1) b0.001IUGR 52 (13.3) 52 (6.6) b0.001Apgar score at 5 min 8.9±0.8 9.0±0.7 0.73Stillbirth 19 (4.8) 6 (0.8) b0.0001Neonatal death 10 (2.6) 8 (1.0) 0.044Perinatal mortality rate 29 (77.7/1000

deliveries)14 (18.0/1000deliveries)

b0.0001

Abbreviations: IUGR, intrauterine growth restriction; SCD, sickle cell disease.a Data are presented as mean±SD or number (percentage) unless otherwise indi-

cated.b χ2 test for frequencies; independent t test for continuous variables.

225M.A. Al Kahtani et al. / International Journal of Gynecology and Obstetrics 119 (2012) 224–226

visit; baseline hematocrit; blood transfusions; and complications.Perinatal and maternal mortality were also recorded.

Electrophoresis was performed at the institutional clinical labora-tory (KKUH) to determine hemoglobin phenotype. In the presentstudy, hemoglobin phenotype was identified as SS (SCD variant) orAA (normal). Gestational age was calculated from the last menstrualperiod as determined by ultrasonography, when available, duringthe first prenatal examination. Sickle cell crisis (SCC) was defined asacute onset of pain episodes requiring immediate medical attentionfor analgesia and intravenous hydration. The KKUH is compliantwith the recommendations set by the Royal College of Obstetriciansand Gynecologists for the management of patients with SCD [9].

Data were analyzed using SPSS version 15.0 (IBM, Armonk, NY,USA). The results are shown as percentages for frequencies, and asmeans and standard deviations for continuous variables. The χ2 testand Fisher exact test were used to compare categoric variablesand the Student t test used for continuous variables exhibiting normaldistribution. A P value below 0.05 was considered statisticallysignificant.

3. Results

A total of 34 811 deliveries occurred during the study period, with392 cases (1.1%) of SCD recorded (data not shown).

Table 1 shows the maternal characteristics of the SCD group ver-sus the control group. The SCD group had a significantly higher prev-alence of prepartum hospital admissions (60.0% vs 18.1%; Pb0.0001)and preterm labor (13.0% vs 5.1%; Pb0.0001) as opposed to the con-trol group. Furthermore, the SCD group had a higher incidence ofpre-eclampsia (9.7% vs 3.2%; Pb0.0001) than the control group. Theother variables measured were comparable (Table 1).

Fetal outcomes are presented in Table 2. Infants of mothers in thecontrol group had a significantly higher mean birth weight than in-fants in the SCD group (Pb0.0001). By contrast, infants from theSCD group had a significantly higher rate of low birth weight (18.6%vs 9.1%; Pb0.001); IUGR (13.3% vs 6.6%; Pb0.001); stillbirths (4.8%vs 0.8%; Pb0.0001); neonatal deaths (2.6% vs 1.0%; P=0.044); andperinatal mortality rate (77.7/1000 vs 18/1000 deliveries; Pb0.0001).

Table 1Maternal characteristics according to the presence or absence of sickle cell disease.a

Characteristic SCD group(n=392)

Control group(n=784)

P valueb

Maternal age, y 23.7±4.4 24.0±3.2 0.18Parity 3.9±2.6 4.1±2.9 0.25Primigravida 182 (46.4) 339 (43.2) 0.30Prenatal visits

1st trimester 172 (43.9) 352 (44.9) 0.742nd trimester 129 (32.9) 231 (29.5) 0.233rd trimester 41 (10.4) 92 (11.7) 0.52

No prenatal care 50 (12.8) 109 (13.9) 0.59Prepartum hospital admission 235 (60.0) 142 (18.1) b0.0001Preterm labor or PROM 51 (13.0) 40 (5.1) b0.0001Term delivery 332 (84.7) 725 (92.5) b0.0001Preterm delivery 60 (15.3) 59 (7.5)PIH or pre-eclampsia 38 (9.7) 25 (3.2) b0.0001Eclampsia 5 (1.3) 6 (0.8) 0.29Gestational diabetes mellitus 48 (12.2) 82 (10.5) 0.36Pyelonephritis 28 (7.1) 27 (3.4) 0.005Route of delivery

Vaginal 316 (80.6) 653 (83.3) 0.26Cesarean 63 (16.1) 105 (13.4) 0.22Instrumental 13 (3.3) 26 (3.3) >0.999

Maternal mortality 2.0 (0.5) 0 (0.0) 0.11

Abbreviations: PIH, pregnancy-induced hypertension; PROM, premature rupture ofmembranes; SCD, sickle cell disease.

a Data are presented as mean±SD or number (percentage) unless otherwise indi-cated.

b χ2 test.

Table 3 shows the complications documented for the SCD group,with anemia accounting to almost 9 out of 10 SCD cases requiringsimple transfusion (33.7%) or exchange transfusion (3.6%). Vaso-occlusive disorders accounted for 43.1% of patients who experiencedSCC. Bacterial infection was documented in 8.8% of cases. The rest ofthe complications noted were minimal.

4. Discussion

The present study uncovered an increased risk of complicationsamong pregnant Saudi women with SCD, as well as increased risk ofmortality and morbidity among infants born to mothers in this group.

Complications of pregnancy examined in the present study includ-ed SCC, anemia, infections, toxemia, IUGR, preterm labor, and repeat-ed hospital admissions, all of which were significantly higher amongthe SCD group than the control group. Nonetheless, the present re-sults suggest that the pregnancy-related complications of SCD en-countered in Saudi Arabia are not as serious as those reported inNigeria [10,11] and the USA [12]. This difference might reflect a pos-sible improvement in the management of SCD in Saudi Arabia; how-ever, this point requires further evaluation [13–15]. The increasedrates of stillbirth and IUGR reported among pregnant women withSCD could be owing to compromised placental blood flow secondary

Table 3Morbidity among the sickle cell disease group, 2001–2010 (n=392).a

Complication Distribution

HematologicSimple transfusion 132 (33.7)Exchange transfusion 14 (3.6)Anemia 338 (86.2)Anemia (Hb b7 g/dL) 123 (31.4)Thrombocytopenia 5 (1.3)

CrisisVaso-occlusive 169 (43.1)Hemolytic 83 (21.2)Aplastic or sequestration 2 (0.5)

CVS and pulmonaryDeep venous thrombosis 6 (1.5)Pulmonary embolism 2 (0.5)Pneumonia and/or pleural effusion 8 (2.1)Acute chest syndrome 4 (1.0)

InfectionUTI, vaginitis, endometritis, cholangitis, osteomyelitis,gastroenteritis, or septicemia

34 (8.8)

Hepatitis virus type A, B, or C 21 (5.3)Hepatobiliary complications

Autosplenomegaly 4 (1.0)Choledocholithiasis 6 (1.5)Gallstones 9 (2.3)

Abbreviations: CVS, cardiovascular system; Hb, hemoglobin; UTI, urinary tract infec-tion.

a Data are presented as number (percentage).

226 M.A. Al Kahtani et al. / International Journal of Gynecology and Obstetrics 119 (2012) 224–226

to maternal vaso-occlusion of the placenta that leads to placental in-farction and insufficient function [16]. The effect of chronic maternalanemia and pregnancy-induced hypertension among patients withSCD further complicates this scenario. By contrast, neonatal mortalityin the SCD group was much lower than previous reports [17,18]. Thematernal mortality rate of 0.5% in the present study was comparablewith the rate of 0.45%–2.50% reported in high-income countries[7,8,19].

Previous studies revealed 2 different forms of SCD that are pre-valent in Saudi Arabia [16,20]; the Asian β globin haplotype, whichis more common in the Eastern region, and the Benin haplotype(African origin), which is more prevalent in the Western region.Clinically, the SCD encountered among patients from the Eastern re-gion of the country has features consistent with elevated hemoglobinF levels and, more frequently, α-thalassemia compared with patientsfrom the Western region, where SCD appears to be more severe[16,20].

In terms of clinical management, prophylactic blood transfusionhas been recommended to reduce SCD-related complications ofchild birth [20]. However, randomized controlled trials reveal no sig-nificant differences in the perinatal outcome between women withvariant hemoglobin (SS) who underwent prophylactic blood transfu-sion and those who did not, with the exception of pain reduction dur-ing SCC in late pregnancy [21,22]. Repeated blood transfusions arefrequently associated with the development of atypical erythrocyteantibodies, which can lead to difficulties in finding compatible bloodwhen it is most needed. Regarding prevention of SCD, the localSaudi government (Ministry of Health) legislated that men andwomen who intend to get married undergo a premarital blood testto exclude hereditary blood disease so that those are potentially atrisk can be provided with the necessary advice with regards to theirfamily planning.

In conclusion, although Saudi women with SCD are at greater riskof maternal and fetal complications than previously reported, suchcomplications are less serious than those reported in other countries.Introducing health education into schools and compulsory premaritalcounseling, including testing for the SCD susceptibility gene, hashelped to achieve this improvement in maternal and neonatal out-comes [23]. A multidisciplinary approach is recommended for thecomprehensive management of pregnant women with SCD.

Conflict of interest

The authors have no conflicts of interest.

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