- Academic Editor
Background: Sickle cell disease (SCD) is one of the most prevalent
genetic disorders, including major SCD and SC Trait (SCT) genotypes.
Many studies have shown a negative association between major SCD and pregnancy.
However, they are underestimated in Cote d’Ivoire statistics. To provide
consistent data on SCD in pregnancy, we compare outcomes between women with
normal hemoglobin (Hb) genotype and major SCD. Methods: A
retrospective, and case-control study in the University Hospital of Cocody, from
2015 to 2018, analyzed maternal and fetal outcomes, comparing the Cases Group:
major SCD (HbSS, HbSC) and Control Group: normal hemoglobin (Hb) genotype A. Only
pregnancies with gestations longer than 28 weeks were included. No cases of
thalassemia or variant of hemoglobin were found. Local protocols recommended
systematic use of vasodilators or analgesics, folic acid, and high concentrations
of inhaled oxygen during labor, associated with fluid and/or blood transfusion.
We excluded sickle cell trait (SCT) genotype AS (HbAS), and incomplete
data. A logistic regression was exploited to gauge the risk factors. We used SPSS
version 19 (IBM Corp., Armonk, NY, USA) for statistical analysis, and calculate
the adjusted odds ratio and 95% confidence interval. Results: We
registered 156 major SCD (0.92%), compared to 312 HbAA. In Cases Group
27.6% were multigravidas (
Normal human hemoglobin (Hb) (HbAA) allows oxygen transfer in blood. Its
chemical structure normally includes one pair of heme molecules (2
We conducted a retrospective cross-sectional and retrospective case-control
study of all hemoglobinopathies at the obstetrics department of the University
Hospital of Cocody (Cote d’Ivoire), between January 2015 and December 2018 (4
years). We have obtained the approval of Felix Houphouet Boigny University for
the publication of the results of this study. This study compared ante, intra and
postnatal outcomes of women with major SCD (Cases Group), to those with normal
hemoglobin genotype or HbAA (Control Group). The inclusion criteria are listed as following:
Cases Group included the major SCD genotypes (HbSS, HbSC), and the Control Group consisted of pregnant women with HbAA.
The exclusion criteria are listed as following: incomplet files lost of follow-up and non consent women.
The genotype was
specified by hemoglobin electrophoresis performed during antenatal care or known
before pregnancy. We analyzed maternal and fetal outcomes. The Cases
Group included the major SCD genotypes (HbSS, HbSC), and the
Control Group consisted of pregnant women with HbAA. No cases of quantitative
sickle cell disorders of globin chains (thalassemia), qualitative disorders of
globin structure, or structural variant of hemoglobin (S-ßthalassemia, HbSF,
HbSD, HbSO) were found in the population. In the same way, we did not find
hemoglobin with decreased stability, and Hemoglobin with altered oxygen affinity
as our laboratories are limited. We obtained consent from 468 pregnant women for
this comparative retrospective study: 156 women with major SCD belonging (Cases
Group); 312 pregnant women with HbAA genotype (Control Group). The
comparison involved ante, intra, and postpartum data, and the selection of the
patient pool was based on matching age, gravidity, and similar socioeconomic
status. Emphasis was on obstetrical history and significant history of the
underlying disease symptomatology. Preterm labor was considered as the onset of
labor before 37 completed weeks of gestation (WG), while anemia was identified
when the hemoglobin concentration level was below 110 g/dL. The World Health Organization (WHO) defined severe
anemia as Hb
Over a 4-year-period, we recorded 16,924 deliveries, with 156 cases of major SCD
(HbSS, 104; HbSC, 52) corresponding to a prevalence of 0.92%. Major SCD forms
included heterozygous genotype (HbSC, 33.3%) and homozygous forms
(HbSS, 66.7%). The mean gestational age at delivery was 36
Data | Cases Group | Control Group | Total | |||
n = 156 (%) | n = 312 (%) | |||||
Age (years) | ||||||
25 | 16.0 | 65 | 20.8 | 90 | ||
21–35 | 88 | 56.4 | 178 | 57.1 | 266 | |
43 | 27.6 | 69 | 22.1 | 112 | ||
Education level | ||||||
Illiterate | 88 | 56.4 | 212 | 67.9 | 143 | |
Educated | 68 | 43.6 | 100 | 32.1 | 157 | |
Profession | ||||||
Informal sector | 52 | 33.3 | 68 | 21.8 | 100 | |
Student | 36 | 23.1 | 132 | 42.3 | 104 | |
Housewife | 68 | 43.6 | 112 | 35.9 | 96 | |
Gravidity (pregnancies number) | ||||||
Primigravida (1) | 34 | 21.8 | 112 | 35.9 | 146 | |
Paucigravida (2–3) | 38 | 24.4 | 97 | 31.1 | 135 | |
Multigravida ( |
84 | 53.8 | 103 | 33.0 | 187 | |
Parity (number of birth) | ||||||
Primiparous (1) | 68 | 43.6 | 77 | 24.7 | 145 | |
Pauciparous (2–3) | 45 | 28.8 | 79 | 25.3 | 124 | |
Multiparous ( |
43 | 27.6 | 156 | 50.0 | 199 | |
Delivery modalities | ||||||
Vaginal delivery | 24 | 15.4 | 198 | 63.5 | 222 | |
Cesarean section | 132 | 84.6 | 114 | 36.5 | 246 |
There was a significant association between major SCD and maternal antenatal
complications, such as
mild anemia (odds ratio (OR) = 64.20, 95% CI [29.62–130.15]; p
Adverse outcomes for mothers | Cases Group | Control Group | Odds Ratio, 95% CI | p | |
n = 156 (%) | n = 312 (%) | ||||
Antenatal complications | |||||
Mild anemia | 98 (62.8%) | 8 (2.6%) | 64.20, [29.62–130.15] | p | |
Preterm births | 64 (62.8%) | 35 (11.2%) | 5.51, [3.42–8.85] | p | |
VOC | 99 (41.0%) | 1 (0.6%) | 540.15, [73.83–3951.59] | p | |
IUGR | 112 (71.8%) | 8 (2.6%) | 96.73, [44.16–211.82] | p | |
PIH | 15 (9.6%) | 77 (24.7%) | 0.33, [0.17–0.58] | p | |
Preeclampsia | 11 (7.1%) | 33 (10.6%) | 0.64, [0.31–1.31] | p = 0.2210 | |
Eclampsia | 7 (4.5%) | 28 (9.0%) | 0.47, [0.20–1.12] | p = 0.0880 | |
Intrapartum complications | |||||
Hemorrhage | 22 (14.1%) | 89 (28.5%) | 0.366, [0.22–0.62] | p = 0.0002 | |
IUFD | 82 (52.6%) | 16 (5.1%) | 20.50, [11.33–37.09] | p | |
CS | 132 (84.6%) | 165 (52.9%) | 4.90, [0.48–1.41] | p | |
Vaginal delivery | 24 (15.3%) | 147 (47.1%) | 0.29, [0.12–0.33] | p | |
Maternal death (MD) | 2 (1.3%) | 19 (6.1%) | 0.20, [0.04–0.84] | p = 0.0320 | |
Postpartum hemorrhage (PPH) | 27 (17.3%) | 75 (24.0%) | 0.66, [0.40–1.08] | p = 0.0978 | |
Morbidity | |||||
Severe anemia | 55 (35.3%) | 24 (7.7%) | 6.53, [3.84–11.10] | p | |
Urinary tract infection | 18 (11.5%) | 16 (5.1%) | 2.25, [1.11–4.54] | p = 0.0235 | |
Painful crisis | 65 (41.7%) | 0 (0.0%) | 272.01, [16.72–4425.09] | p | |
Blood transfusion | 67 (42.9%) | 65 (20.8%) | 373.32, [22.87–6093.85] | p | |
Acute chest syndrome | 12 (7.7%) | 1 (0.3%) | 25.91, [3.33–201.23] | p = 0.0019 |
VOC, vaso-occlusive crisis; IUGR, intrauterine growth restriction; PIH, pregnancy-induced hypertension; CS, cesarean section; CI, confidence interval; IUFD, in-utero fetal distress or death.
Logistic regression analysis did not confirm a statistically significant
association between the major SCD group and HbAA, concerning CS (p
Adverse outcomes for the fetus | Cases Group | Control Group | Odds ratio, 95% CI | p |
n = 156 (%) | n = 312 (%) | |||
Live birth | 142 (91.0%) | 220 (70.5%) | 4.24, [2.32–7.74] | p |
Low birth weight (LBW) | 112 (71.8%) | 24 (7.7%) | 30.54, [17.74–52.58] | p |
Apgar score at |
62 (39.7%) | 43 (13.8%) | 4.12, [2.61–6.49] | p |
Stillbirth or neonatal mortality | 8 (5.1%) | 15 (4.8%) | 0.34, [0.27–1.53] | p = 0.3150 |
Acute fetal distress (AFD) | 27 (17.3%) | 53 (17.0%) | 1.02, [0.61–1.70] | p = 0.9308 |
Intrauterine fetal death (IUFD) | 6 (3.8%) | 10 (3.2%) | 1.21, [0.43–3.39] | p = 0.7194 |
Neonatal infection | 7 (4.5%) | 25 (8.0%) | 0.53, [0.23–1.28] | p = 0.1600 |
Perinatal mortality | 12 (7.7%) | 15 (4.8%) | 1.65, [0.75–3.61] | p = 0.2110 |
The main morbidity was severe anemia in major SCD (35.3%) when compared to HbAA
(7.7%) (p
Sickle cell disease (SCD), first described three centuries ago in Africa [6, 11], is an autosomal recessive disorder with higher maternal and fetal risk
during pregnancy [12, 13]. People who inherited one copy of the HbS
allele, and one normal HbA allele (HbAS), also called sickle
cell trait (SCT), are typically asymptomatic, with no serious adverse outcomes
[12]. The homozygous form of the HbS gene (HbSS) characterizes sickle
cell anemia, the most prevalent monogenic condition worldwide [1, 2, 13, 14, 15, 16, 17, 18].
However, other genotypes causing SCD can be identified, corresponding to
the uniparental inheritance of the
There are some limitations in the present study. This was a retrospective study based on patients’ data collected at a hospital and further analyzed. Our study did not cover women with SCD who delivered at home or other health care facilities in the territory, as well as the cause of the perinatal mortality rate of 4.4% observed in the Control Group (p = 0.50). Therefore, the findings of this study may not be generalized to all the women in Cote d’Ivoire. Prospective data collection could increase the quality and credibility of the presented results. Nevertheless, our results were reported according to statistical standards that would minimize potential bias. Also, we did not perform a statistical comparison between data of the different sickle cell genotypes which could have allowed us to determine prognostic factors. This will soon be done in a prospective cohort multi-centric study.
The findings of the present survey suggest better fetal and maternal prognosis in HbAA, than in major SCD. The latter is associated with maternal complications, such as severe anemia, low birth weight, and prematurity. Multidisciplinary team management is required during these pregnancies to improve maternal and fetal prognosis. Patient awareness and education, and early and effective prenatal care are useful to avoid those risks.
Data supporting the results of this study are available from the corresponding author, but restrictions apply to their availability. The data were used under license for the current study, and are therefore not publicly available. However, the data are available from the authors upon reasonable request and with permission from Mian et al.
VAA, JK, KHY contributed to the extraction and drafting this manuscript; data analysis, design and editing. DBM, VAA, CJN, JK, KNG, SB have made the final statistical analysis and manuscript revision. All authors have read and approved this final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.
The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Felix Houphouet Boigny University (N245354-CI/2020). All subjects gave their informed consent for inclusion before they participated in the study.
We acknowledge any support provided that is not covered by the authors’ contribution.
This research received no external funding.
The authors declare no conflict of interest.
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