|Year : 2019 | Volume
| Issue : 1 | Page : 1-7
Towards zero mortality in sickle cell pregnancy: A prospective study comparing haemoglobin SS and AA women in Lagos, Nigeria
Ochuwa Adiketu Babah1, Monsurat Bolanle Aderolu2, Ayodeji A Oluwole1, Bosede B Afolabi1
1 Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medicine, University of Lagos; Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria
2 Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Idi-Araba; Department of Obstetrics and Gynaecology, Alimosho General Hospital, Igando, Lagos, Nigeria
|Date of Web Publication||12-Mar-2019|
Ochuwa Adiketu Babah
P.M.B 12003, Lagos University Teaching Hospital, Surulere, Lagos
Source of Support: None, Conflict of Interest: None
Introduction: Sickle cell disease in pregnancy carries increased risk of maternal and perinatal morbidity and mortality. Past studies on pregnancy complications in sickle cell disease women were limited by relatively small sample sizes, and use of retrospective and hospital discharge data. Study Design: This prospective case-control study compared booked pregnant Haemoglobin (Hb) SS women with AA controls from two tertiary centres in Lagos, in order to precisely identify their complication and mortality rates and identify associated factors. Eligible pregnant HbSS and HbAA women were recruited from antenatal clinics at booking and follow-up visits. Information was collected on a proforma and data was analyzed using IBM SPSS version 20. Results: We found higher complication rate in HbSS group, commonest complications being vaso-occlusive crisis (RR 1.47, 95% CI 1.22 – 1.78), pregnancy induced hypertension (RR 1.31, 95% CI 1.08 – 1.57), urinary tract infection (RR 1.32, 95% CI 1.12 – 1.57), and intrauterine growth restriction (RR 1.2, 95% CI 1.05 – 1.34). HbSS group had higher systolic and mean arterial blood pressure values in early puerperium compared to HbAA group (p = 0.014 and 0.024 respectively). No maternal death recorded in both group. Incidence of low birth weight <2.5Kg was 38% in HbSS and 4% in HbAA subjects, p = 0.001. However, overall maternal and perinatal outcomes were comparable in both groups (p = 1.000). Conclusion: Although sickle cell disease poses higher obstetric risk in pregnancy, maternal and perinatal outcome can be as good as in the non-sickle cell pregnant women if adequate and prompt individualized care is given to this group of women.
Keywords: Complications, haemoglobin AA, haemoglobin SS, maternal outcome, perinatal outcome, sickle cell disease pregnancy
|How to cite this article:|
Babah OA, Aderolu MB, Oluwole AA, Afolabi BB. Towards zero mortality in sickle cell pregnancy: A prospective study comparing haemoglobin SS and AA women in Lagos, Nigeria. Niger Postgrad Med J 2019;26:1-7
|How to cite this URL:|
Babah OA, Aderolu MB, Oluwole AA, Afolabi BB. Towards zero mortality in sickle cell pregnancy: A prospective study comparing haemoglobin SS and AA women in Lagos, Nigeria. Niger Postgrad Med J [serial online] 2019 [cited 2019 Jul 20];26:1-7. Available from: http://www.npmj.org/text.asp?2019/26/1/1/253979
| Introduction|| |
Sickle cell disease (SCD) is the most common inherited disease worldwide, with 75% of cases in Sub-Saharan Africa. In Nigeria, about 24% of the population carry the sickle cell trait and approximately 150,000 children are born annually with sickle cell anaemia, with a prevalence of 2% of newborns affected by sickle cell anaemia.
The World Health Organisation at the 59th World Health Assembly in 2006 estimated that half of SCD patients in Sub-Saharan Africa will die before adulthood., However, with improvement in the health-care system in recent years and increased childhood survival, more women with SCD are seen growing into adulthood and presenting for antenatal care. Considering the burden sickle cell anaemia poses in pregnancy, there is a need to have a clearer understanding of the pattern of pregnancy complications to which SCD women are predisposed.
There are discrepancies in the findings of earlier studies on pregnancy complications in SCD. Several studies reported complications such as anaemia, gestational hypertension, pre-eclampsia, severe crises, post-partum haemorrhage, pulmonary diseases, maternal infection, preterm delivery, increased incidence of low birth weight and foetal distress in labour as being prevalent, with an increased perinatal mortality.,,, Afolabi et al. in an earlier study in Lagos, Nigeria did not identify preeclampsia as a predominant complication and Odum et al. in another study in Lagos, Nigeria did not identify it as a complication in sickle cell pregnancies. Surprisingly, pre-eclampsia and urinary tract infection were observed more in haemoglobin (Hb) AS than HbSS women in other studies., Most of these studies were retrospective, and it is our belief that this prospective study would help us clarify some of these discrepancies.
In a meta-analysis by Oteng-Ntim et al., it was observed that pregnant women with SCD were at higher risk for complications including pre-eclampsia compared to the general population even in developed countries with advanced care and that women with the most severe form of SCD were six times more likely to die during or shortly after pregnancy. Blood pressure has been reported to be lower in sickle cell individuals, although Obilade et al. did not find this in their study on pregnant women with SCD. With a good knowledge of the pattern of blood pressure and incident complications in pregnant SCD women in our environment, we will be able to promptly anticipate and identify complications arising in pregnancy, during delivery and puerperium. We will also institute measures to reduce the incidences of near miss, which was found to be as high as 33% by Resende Cardoso et al.
Reports of maternal and foetal deaths continue to alternate with descriptions of entirely uneventful pregnancies. Low- and middle-income countries generally report increased maternal and perinatal morbidity and mortality in association with SCD., Studies in high-income countries report more favourable foetal outcomes without appreciable risk for increased maternal morbidity., Earlier studies done in Lagos, Nigeria had maternal death rates of 5.3% and 6.6% among pregnant women with SCD.,
The objectives of this study were to compare the incidence of complications, maternal and foetal outcome such as admissions and mortality and to determine factors affecting the foetomaternal outcome in pregnant HbSS women compared to HbAA.
| Methodology|| |
This was a prospective comparative study of HbSS and HbAA pregnant women conducted between October 2014 and December 2015.
The study was conducted at the Department of Obstetrics and Gynaecology of Lagos University Teaching Hospital, Idi Araba (LUTH), Lagos, Nigeria, and Lagos State University Teaching Hospital, Ikeja (LASUTH), Lagos, Nigeria. This study had the approval of the Health Research and Ethics Committee of Lagos University Teaching Hospital (Approval number ADM/DCST/HREC/1768) and Health Service Committee for Lagos State Hospitals to utilise Lagos State University Teaching Hospital patients for the study (Approval number SHMB/728/Vol. VI/).
The study population comprised pregnant women who booked and had antenatal care and delivery at the study centres. A total of 100 pregnant women were studied based on sample size calculation, of which 50 with HbSS genotype served as cases and 50 with HbAA genotype served as control.
Selection of patients
Every consenting HbSS woman that met the study criteria was recruited. Similarly, the next presenting HbAA woman matched for age, parity and gestational age at booking was recruited at each antenatal clinic as a control.
Selection based on age was done using age grouping as follows: 16–20, 21–25, 26–30, 31–35, 36–40 and 41–45 years. Parity was categorised as follows: Para 0, Para 1, Para 2–4 and Para 5 and above. Gestational age at booking was grouped as follows: 12–16, 17–20, 21–24, 25–28, 29–32, 33–36 and 37–42 weeks.
Included in this study were pregnant women between the age range of 18 years–45 years and pregnant women with genotype HbSS and HbAA diagnosed in LUTH and LASUTH. Those excluded were women with diabetes mellitus, renal failure, heart diseases, chronic essential hypertension, human immunodeficiency virus-positive and other medical disorders and women with multiple gestations.
Sample size determination
Given a prevalence of 45.5% for preterm deliveries in SCD pregnancy and 17.7% in non-SCD in a previous study, the minimum sample size required to give a power of 80% at a confidence level of 95% was calculated to be 40, using the formula for calculating sample size when comparing proportions between two independent groups, n = (Zα/2+ Zβ)2 × (p1[1 − p1] + p2[1 − p2])/(p1− p2)2.
n = 39.9, which is approximately 40.
We considered a 20% attrition rate which was 8, thereby making the minimum sample size required for this study 48 in each group. We however recruited 50 per group for this study.
Structured questionnaires were used to obtain participants' personal information at booking after counselling and having obtained written consent. The participants' phone numbers were collected, and the investigator's phone number was given to the women. The women were informed to call the investigator anytime they were admitted into the hospital. They were also called every week to enquire about their health. They were seen in the labour ward or antenatal ward to get other information from them, and from their case notes, whenever they were on admission. Information obtained included the number of antenatal visits, packed cell volume, any previous crises and treatment for urinary tract infection, chest infection and anaemia. While in labour, their blood pressures were measured using a digital blood pressure monitor (Microlife 3BTO-A blood pressure monitor). Blood pressure was recorded in the first and second stages of labour, immediate post-partum and 6-h post-partum. The SpO2 was also monitored whenever they were on admission and in labour. The blood loss at delivery was estimated by visual assessment. They were also seen while in the post-natal ward to update their information.
The primary outcome measures were maternal indices such as incidence of hypertensive disorders in pregnancy, incidence of urinary tract infections, caesarean section rates, incidence of post-partum haemorrhage, pseudotoxaemia, incidence of retained placenta, wound status and incidence of puerperal complications such as breast engorgement and perinatal indices such as birth weight, APGAR score, incidence of stillbirth and neonatal unit admission rate. We defined pseudotoxaemia in this study as a combination of albuminuria and systolic hypertension occurring during a bone pain crisis. We also defined foetal outcome as delivery of a live baby or stillbirth in this study.
The secondary outcome measures were average blood pressure in mmHg, during labour and in the puerperium, frequency of admission, gestational age at delivery, duration of labour and blood loss at delivery.
All data collected were subjected to statistical analysis using SPSS version 20 (IBM corp., USA). The Chi-square test was used in comparing categorical variables where applicable and Fischer's Exact test was used where an expected value is <5. General Linear Model Univariate Analysis of Variance to assess factors that can influence maternal outcome such as maternal age, parity, gestational age at booking, blood pressures in during labour and puerperium, duration of labour and estimated blood loss at delivery. It was also used to assess factors affecting foetal outcome. The Pearson's Product-Moment Correlation Coefficient was used in assessing correlation between maternal weight and foetal birth weight after testing for normality of the population distribution. P < 0.05 was considered to be statistically significant. Socioeconomic status was determined using the occupation of subject and that of her husband, using the National Readership Survey grades.
| Results|| |
The mean age ± standard error of mean of the participants was 29.84 ± 0.431 years. They were all booked women. Majority (38%) booked after 16 weeks but before 20 weeks gestational age, with only 10% booking before 16 weeks, while 4% of the women booked late in pregnancy after 32-week gestational age. [Table 1] shows details of the participants' demographic characteristics. Complications occurred significantly more frequently in HbSS pregnant women compared to HbAA pregnant women (92% and 38%, respectively, P = 0.001, relative risk [RR] =7.750, confidence interval [CI] 2.9535–20.3361). [Table 2] summarises the incidence and pattern of complications in each group.
|Table 2: Incidence of complications in haemoglobin AA and haemoglobin SS parturient|
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Admissions were significantly more frequent in the HbSS pregnant women (P = 0.001). The incidence of preterm delivery was significantly more in the HbSS compared to HbAA group (P = 0.022). The caesarean section rate was higher in HbSS than HbAA group (80% versus 34%), most being conducted as emergencies. For those who had normal delivery, it was found that the duration of second stage of labour was significantly longer in the HbSS compared to the HbAA parturient with a mean difference of 38.33 minutes, P = 0.003. [Table 3] summarises these findings. Of the 50 HbSS women studied, 13 (26%) had blood transfusion while 2 of the 50 HbAA (4%) studied had blood transfusion (P = 0.002, RR = 1.2973, CI 1.0904–1.5435). There was no maternal death recorded in either group in this study.
|Table 3: Maternal outcome in haemoglobin AA and haemoglobin SS parturient|
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Although there was no significant difference in average blood pressure values during the first and second stage of labour, the HbSS group had significantly higher mean systolic BP and mean arterial blood pressure (MAP) values at 6-h post-partum compared to the HbAA group (P = 0.014 and 0.024, respectively). The details of these findings are summarised in [Table 4].
|Table 4: Blood pressure pattern in labour and early puerperium in haemoglobin AA and haemoglobin SS women|
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HbSS women are more likely to have lighter babies than the HbAA women, mean ± standard deviation of birth weight of 2.56 ± 0.62 kg and 3.23 ± 0.52 kg, respectively, P = 0.001. The incidence of low birth weight below 2.5 kg was 38% in HbSS and 4% in HbAA participants (P = 0.001). We further assessed the correlation between maternal weight and foetal birth weight in both groups combined, and we found a weak positive but statistically significant correlation between the two parameters, r = 0.333, P = 0.001. There was also a moderate positive correlation between gestational age at delivery and foetal birth weight, r = 0.653, P = 0.001. After adjusting for maternal weight and gestational age at delivery, the difference in foetal weight between the two groups was found to be statistically significant (P = 0.003).
The HbSS has a higher incidence of birth asphyxia defined by APGAR score <7 in this study. At 1 min, the proportion of HbSS and HbAA with APGAR score <7 was 25/49 (51.0%) versus 5/49 (10.2%), respectively, P = 0.001, while at 5 min, the incidence reduced to 5/49 (10.2%) versus 0/49 (0.0%), respectively, P = 0.001. The HbAA group had median APGAR scores of 8 at 1 min and 9 at 5 min, while the HbSS group had median APGAR scores of 6 at 1 min and 8 at 5 min. Neonatal unit admission rate was significantly higher for the HbSS babies compared to the HBAA group, 21/50 (42%) versus 2 (4%), respectively, P = 0.001. Perinatal death was comparable in both groups, live births were 49 (98%) and stillbirths 1 (2%) in each group, P = 1.000, odds ratio = 1.000, 95% CI = 0.061–16.444.
Factors that can influence maternal outcome such as maternal age, parity, gestational age at booking, blood pressures in during labour and puerperium, duration of labour and estimated blood loss at delivery were assessed, and it was found that when a combined assessment of both groups was done, only MAP at 6-h post-delivery (P = 0.039) and estimated blood loss at delivery (P = 0.022) significantly influence maternal outcome. This association remained similar in the HbAA group only with MAP at 6-h post-delivery (P = 0.034) and estimated blood loss at delivery (P = 0.017) being statistically significant. Statistical significant was however lost in HbSS group (P = 0.105 for MAP at 6-h post-delivery and P = 0.076 for estimated blood loss).
There was no statistically significant relationship between maternal age and foetal outcome (P = 0.725) or between parity and foetal outcome (P = 0.084), but there was a statistically significant relationship between gestational age at delivery and foetal outcome when both groups were assessed together (P = 0.001) and when each group was assessed alone (HbSS group, P = 0.021 and HbAA group, P = 0.001). Only average diastolic blood pressure in the first stage of labour showed statistically significant relationship with foetal outcome in both groups combined (P = 0.001) and in HbAA only (P = 0.001).
| Discussion|| |
In comparison with earlier studies, we found a higher complication rate in the HbSS pregnant women compared to their HbAA counterparts, reiterating the fact that pregnancy in HbSS women is high risk. The most common complications in HbSS pregnant women as observed in this study were vaso-occlusive (bone pain) crises (32%), pregnancy-induced hypertension (28%), malaria (18%), intrauterine growth restriction (16%) and urinary tract infection (13%). The incidence of bone pain crisis in this study is slightly higher than was reported in an earlier study by Afolabi et al. in this centre in 1996–2000 (25.3%) but much lower than the incidence reported by Resende Cardoso et al. (77.8%). The lower prevalence reported in our centre previously might be because it was a retrospective study, which unlike prospective studies may not give room for adequate data collection or maybe as a result of environmental differences.
We also found higher incidences of pregnancy-induced hypertension, preterm delivery, intrauterine growth restriction and urinary tract infection in the HbSS pregnant women compared to their HbAA counterparts. This observation is similar to findings in other studies.,,, The three HbSS patients who had acute chest syndrome were admitted into the intensive care unit, managed by partial exchange blood transfusion, oxygen supplementation, good hydration, antibiotic coverage and aggressive pulmonary therapy.
The proportion of women with gestational hypertension and pre-eclampsia was higher in the HbSS group than the HbAA group in this study. It has been established that women with SCD have lower ratio of prostacyclin/thromboxane, and this may indicate an increased tendency to vasoconstriction and may explain why HbSS women are more prone to developing hypertensive disorders in pregnancy compared to non-SCD women.
The difference in the incidence of gestational hypertension in the two groups studied was statistically significant. However, there was a loss of statistical significance in the incidence of pre-eclampsia when both groups were compared. This might be because this study was not specifically power for pre-eclampsia. Granger et al. in an earlier study found a reduction in utero placental circulation to be a vital initiating event in the development of pregnancy-induced hypertension, and it was thought that placental ischaemia may play a role. In subsequent studies, it was established that placental ischaemia is not a causal factor in pre-eclampsia but a consequence of the disease., This may further explain why there was a statistically significant difference in the incidence of gestational hypertension in HbSS women compared to HbAA group but not so with pre-eclampsia, as SCD is association with recurrent plugging of blood vessels by sickled cells which causes ischaemia and can result in a reduction in utero placental circulation, thus increasing the risk of gestational hypertension.
HbSS women had a higher incidence of preterm delivery probably because of a higher complication rate in them, which led to early delivery. The incidence of preterm birth among HbSS and HbAA group in this study was 28% and 10%, respectively. A recent meta-analysis found that preterm delivery was more than twofold increased risk in women with HbSS compared to women without SCD.
Unlike several studies that have reported an increased incidence of spontaneous miscarriages and ectopic pregnancy in HbSS pregnant women, this study did not record any of these complications, probably because the women were recruited late to detect these complications.,, None of the women recruited was lost to follow-up probably because adequate counselling was given at the time of recruitment and most of the women were also educated.
This study did not report any maternal death, unlike previous studies.,,,, Majority of the HbSS women were recruited from LUTH, and about 80% of them were managed by one of the authors. The other institution that the remaining women were recruited from is also a tertiary institution. The fact that the women had no additional comorbidities may also have contributed to the favourable prognosis. However, the women with SCD studied in the past suffered mortalities from complications developed during pregnancy and not from co-morbidities.,
There was also no increased risk of IUFD in both groups which is similar to the findings in some previous studies, probably due to improved foetal monitoring and prompt intervention. Low birth weight is one of the most consistent findings in neonates born to mothers with SCD.,, Almost half of the neonates in this study were of low birth weight which reflected in the number of neonatal unit admission. We found an increased risk of Apgar score below 7 at 1 min, but there was no difference at 5 min. This is likely to be a reflection of the neonatal care offered to these groups of patients as they were managed in tertiary institution. There was no neonatal death reported in both groups studied.
Contrary to earlier reports that blood pressure tends to be lower in HbSS individuals, this study found a slight increase in blood pressure in labour in HBSS compared to HbAA women, with a significant fall in the MAP in early puerperium in HbSS women. The reason for this is unknown. However, bearing in mind the fact that systolic blood pressure is commonly affected by emotional issues, anxiety and stress, we presume that the increase in blood pressure in labour in HbSS parturient may be attributable to the higher level of anxiety and stress that labour and delivery pose on this group of women. It is thus advisable to shorten second stage of labour in this group of parturient.
Despite the increased complication rates reported among HbSS pregnant women compared to their HbAA counterpart as reported in this study, the overall maternal and perinatal outcomes were comparable in both groups probably because of the individualised care and close monitoring.
This study is however limited by the possibility that some patients may have chronic undiagnosed medical conditions such as early-stage renal disease and Class I heart disease which may be asymptomatic at recruitment. Second, some of the outcome measures such as estimated blood loss at delivery are subjective and liable to observer error as assessment was done by visual inspection. However, this study is strengthened by the prospective recruitment of 50 pregnant women with SCD and controls that were carefully matched.
| Conclusion|| |
Complications found in this study were comparable to some earlier studies. In addition, prolonged second stage and increased MAP and systolic BP in the puerperium were new findings. However, although SCD poses higher obstetric risk in pregnancy, the maternal and perinatal outcomes can be as good as in the non-SCD pregnant women if adequate and prompt healthcare is given to this group of women, especially where adequate workforce exists to offer them individualised care. This will also promote awareness of the disease among affected women and encourage them to present early for booking, assessment and appropriate management of symptoms.
Financial support and sponsorship
The cost of the research was borne solely by the authors.
Conflicts of interest
There are no conflicts of interest.
| References|| |
McGann PT, Hernandez AG, Ware RE. Sickle cell anemia in sub-Saharan Africa: Advancing the clinical paradigm through partnerships and research. Blood 2017;129:155-61.
World Health Organization. Sickle-Cell Anaemia Report by the Secretariat. Fifty-Ninth World Health Assembly, A59/9 Contract No.: Provisional Agenda Item 11.4. World Health Organization; 2006a.
Asnani MR, McCaw-Binns AM, Reid ME. Excess risk of maternal death from sickle cell disease in Jamaica: 1998-2007. PLoS One 2011;6:e26281.
Cunningham FG, Kenneth JL, Steven IB, John CH, Dwight JR, editors. Hematological Disorders. Williams Obstetrics. 23rd
ed. McGraw-Hills Companies Inc., USA. 2010. p. 1079-103.
Oteng-Ntim E, Chase AR, Howard J, Anionwu EN. Sickle cell disease in pregnancy. Obstet Gynaecol Reprod Med 2008;18:272-8.
Smith JA, Espeland M, Bellevue R, Bonds D, Brown AK, Koshy M, et al.
Pregnancy in sickle cell disease: Experience of the cooperative study of sickle cell disease. Obstet Gynecol 1996;87:199-204.
Acharya N, Kriplani A, Hariharam C. Study of perinatal outcome in pregnancy with sickle cell disease. Int J Biol Med Res 2013;4:3185-8.
Afolabi BB, Iwuala NC, Iwuala IC, Ogedengbe OK. Morbidity and mortality in sickle cell pregnancies in Lagos, Nigeria: A case control study. J Obstet Gynaecol 2009;29:104-6.
Odum CU, Anorlu RI, Dim SI, Oyekan TO. Pregnancy outcome in HbSS-sickle cell disease in Lagos, Nigeria. West Afr J Med 2002;21:19-23.
Sonwane AS, Zodpey SP. Pregnancy outcome in women with sickle cell disease/trait. J Obstet Gynecol India 2005;55:415-8.
Oteng-Ntim E, Meeks D, Seed PT, Webster L, Howard J, Doyle P, et al.
Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: Systematic review and meta-analysis. Blood 2015;125:3316-25.
Obilade OA, Akanmu AS, Broughton Pipkin F, Afolabi BB. Prostacyclin, thromboxane and glomerular filtration rate are abnormal in sickle cell pregnancy. PLoS One 2017;12:e0184345.
Resende Cardoso PS, Lopes Pessoa de Aguiar RA, Viana MB. Clinical complications in pregnant women with sickle cell disease: Prospective study of factors predicting maternal death or near miss. Rev Bras Hematol Hemoter 2014;36:256-63.
Sun PM, Wilburn W, Raynor BD, Jamieson D. Sickle cell disease in pregnancy: Twenty years of experience at Grady memorial hospital, Atlanta, Georgia. Am J Obstet Gynecol 2001;184:1127-30.
Muganyizi PS, Kidanto H. Sickle cell disease in pregnancy: Trend and pregnancy outcomes at a tertiary hospital in Tanzania. PLoS One 2013;8:e56541.
Desai G, Anand A, Shah P, Shah S, Dave K, Bhatt H, et al.
Sickle cell disease and pregnancy outcomes: A study of the community-based hospital in a tribal block of Gujarat, India. J Health Popul Nutr 2017;36:3.
Wang H, Chow S. Sample Size Calculation for Comparing Proportions. Wiley Encyclopedia of Clinical Trials. Sec 3.1. John Wiley & Sons Inc., USA. 2007;3-4.
Hendrickse JP, Watson-Williams EJ. The influence of haemoglobinopathies on reproduction. Am J Obstet Gynecol 1996;94:739-48.
Wilmshurst J, Mackay A, editors. NRS social grade. The Fundamentals of Advertising. 2nd
ed. London: Routledge Taylor and Francis Group; 1999. p. 209-17.
Serjeant GR, Loy LL, Crowther M, Hambleton IR, Thame M. Outcome of pregnancy in homozygous sickle cell disease. Obstet Gynecol 2004;103:1278-85.
Nana OW, Fatouk C, Jacqueline MH, Adel D, Samuel AO, Adjei AA, et al
. Pregnancy outcome among patients with sickle cell disease at Korle-Bu teaching hospital, Accra, Ghana. Am J Med Hyg 2012;86:936-42.
Granger JP, Alexander BT, Bennett WA, Khalil RA. Pathophysiology of pregnancy-induced hypertension. Am J Hypertens 2001;14:178S-85S.
Roberts JM. Pathophysiology of ischemic placental disease. Semin Perinatol 2014;38:139-45.
Ayuk PT, Matijevic R. Placental ischaemia is a consequence rather than a cause of pre-eclampsia. Med Hypotheses 2006;67:792-5.
Olujohungbe A, Howard J. The clinical care of adult patients with sickle cell disease. Br J Hosp Med (Lond) 2008;69:616-9.
Zia S, Rafique M. Comparison of pregnancy outcomes in women with sickle cell disease and trait. J Pak Med Assoc 2013;63:743-6.
Villers MS, Jamison MG, De Castro LM, James AH. Morbidity associated with sickle cell disease in pregnancy. Am J Obstet Gynecol 2008;199:125.e1-5.
Ugboma HA, George IO. Sickle cell disease in pregnancy: Maternal and fetal outcome in Port Harcourt, Nigeria. Br J Med Med Res 2015;7:40-4.
Berzolla C, Seligman NS, Nnoli A, Dysart K, Baxter JK, Ballas SK. Sickle cell disease and pregnancy: Does outcome depend on Genotype or Phenotype. Int J Clin Med 2011;2:313-7.
Hasell K, Karovitch A. Haemoglobinopathies, thalassemias and anaemia. In: Rosene-Montella K, Barbour LA, Richard VL, editors. In Medical Care of the Pregnant Patient. 2nd
ed. United States of America: Sheridan Press; 2008. p. 486-97.
[Table 1], [Table 2], [Table 3], [Table 4]