Maternal and Perinatal Prognosis of Pregnancies in Women with Sickle Cell Disease at Chud-B/A from 2019 to 2023 ()
1. Introduction
Sickle cell disease (SCD) is the most common monogenic disease worldwide [1] [2]. Over the past four decades, notable advances have made it possible to improve the survival of patients with sickle cell disease in both developed and low-resource countries. The corollary of this is a substantial increase in the number of subjects of childbearing age. However, the association between sickle cell disease and pregnancy is a risky situation for the mother, the fetus and even the neonate. Pregnant women with sickle cell disease are known to be at high risk of obstetric complications and perinatal mortality as well as sickle cell disease-related complications [1] [2]. Complications such as vaso-occlusive crises (VOC), acute chest syndrome (ACS), exacerbation of pre-existing anemia, and thromboembolic events are more important during pregnancy [2]. Fetal and neonatal complications include, among others: intrauterine growth retardation (IUGR), acute fetal asphyxia (AFA), prematurity and high perinatal mortality. Unlike in developed countries, the management of these pregnant women is a real challenge due to the increased risk of complications. In Africa, the prevalence of maternal mortality among pregnant women varies between 0.38 - 1.29/100,000 births and that of perinatal mortality between 1.21 - 2.5/100,000 births [3].
In Benin, the prevalence of major sickle cell disease (HbSS) is estimated at 4.18% [4] and 25% of subjects carry the S trait [3]. Taking into account factors predicting complications could improve patient care in order to reduce their mortality.
In Parakou, in a hospital study carried out at CHUD-Borgou/Alibori, the frequency of sickle cell disease among pregnant women was 1.3%, maternal mortality at 42‰ and perinatal mortality at 243.5‰ [3] [5]. The prognostic aspects of the maternal and perinatal prognosis have been addressed little in this previous study. That’s why the objective of this work will be to study the maternal and perinatal prognosis in pregnant women with sickle cell disease.
Site and study methods
This was a case-control study, carried out in the maternity and neonatology departments of the Regional Teaching Hospital of Borgou/Alibori (CHUD-B/A), from January 1, 2019 to June 30, 2023.
The study population consisted of all pregnant women with major sickle cell syndromes, those without sickle cell disease who gave birth at CHUD-Borgou/Alibori and their neonates.
Were included in the study:
-Cases: pregnant women suffering from major sickle cell syndrome (SS, SC, Sβ thalassemia), confirmed by hemoglobin electrophoresis, having given birth at the maternity ward of CHUD-Borgou/Alibori at the end of 22 weeks of amenorrhea (WA) or more or to a neonate alive or dead at birth weighing at least 500 g.
- Controls: pregnant women without sickle cell disease with a phenotype AA confirmed by hemoglobin electrophoresis, having given birth at the maternity ward of CHUD-Borgou/Alibori at the end of 22 WA or more or to a living or deceased neonate at birth weighing at least 500 g.
Were excluded from the study:
- Pregnant women whose medical records were unusable and incomplete;
- Pregnant women with comorbidities such as human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), diabetes and preconception hypertension.
- Matching criteria
Each pregnant woman with sickle cell disease was matched with two (2) non-sickle cell pregnant women according to age criteria (<20 years, 20 to 29 years; 30 to 39 years and ≥40 years); parity (nulliparous and primiparous, pauciparous, multiparous and grand multiparous) and gestational age (22 - 28 WA, 28 WA to 34 WA, 34 WA to 36 WA +6 days and ≥37 WA).
The pregnancy was considered well-monitored when the pregnant woman had completed at least 8 quality antenatal consultations as recommended by WHO [6].
Anemia in mothers was considered severe for a hemoglobin level below 7g/dl according to WHO criteria [6].
The sampling consisted of a systematic recruitment of all medical records of eligible pregnant women according to our inclusion criteria.
The minimum sample size calculated using the Schwartz formula was 62.
Maternal prognosis was the dependent variable. It is good or bad.
It was considered poor maternal prognosis, the occurrence of at least one complication and/or maternal death during pregnancy, delivery or after delivery.
The central tendency and dispersion parameters (mode, mean, median, standard deviation) were used to describe the quantitative variables. Proportions with their confidence interval (CI) were used for qualitative variables. The Chi (X²) statistical test was used to compare the frequency of maternal and perinatal complications according to the modalities of the independent (qualitative) variables. The difference was statistically significant for a p-value less than 0.05. The protocol was submitted to the local ethics committee for biomedical research at the University of Parakou (CLERB-UP).
2. Results
Out of a total of 11,212 pregnant women admitted, 153 pregnant women with sickle cell disease were identified at the maternity ward of CHUD-Borgou/Alibori from January 2019 to June 31, 2023 and 127 had a usable medical record. The frequency of pregnant women with sickle cell disease was 1.36% (153/11212). Heterozygous pregnant women (HbSC) were the most represented, i.e., 77.2% (98/127).
Age of the pregnant women with sickle cell disease
The average age of the sickle cell pregnant women was 26.77 years ± 5.03 with extremes of 18 and 40 years. Pregnant women aged between 25 and 30 years were the most represented (37%). Pregnant women aged under 20 years, between 20 and 24 years, between 30 and 34 years and over 35 years old were 3.9%, 30.7%, 16.5%, and 11.8%, respectively.
Complications during the current pregnancy in the 2 groups of pregnant women
VOC was the main complication observed in pregnant women with sickle cell disease during pregnancy (26%). No pregnant woman had an acute chest syndrome.
Regarding the complications common to the two groups of pregnant women, urinary tract infections (18.1%), severe anemia (22.8%), severe malaria (26.8%) were more reported in sickle cell women than in non-sickle cell women in whom they represented 0.8%, 2% and 0.4%, respectively. The difference was statistically significant in all cases (p-value = 0.000).
In terms of fetal and adnexal complications, IUGR and the threat of premature birth (TPB) were predominant in sickle cell pregnant women with 3.9% and 4.7% of cases, respectively compared to 1.6% and 3.2% of cases, respectively in pregnant women without sickle cell disease. The difference is not significant (Table 1).
Table 1. Distribution of sickle cell and non-sickle cell pregnant women according to complications specific and non-specific to sickle cell disease occurring during pregnancy at CHUD-B/A from 2019 to 2023.
|
Type of patient |
p-value |
With SCD |
Without SCD |
n |
% |
n |
% |
Complications specific to SCD |
|
|
|
|
|
VOC |
33 |
26.0 |
- |
- |
|
ACS |
0 |
0.0 |
- |
- |
|
Non-specific complications of SCD |
|
|
|
|
|
Gestational hypertension |
18 |
14.2 |
45 |
17.9 |
0.621 |
Premature rupture of membranes |
16 |
12.6 |
35 |
13.9 |
0.749 |
Oligohydramnios |
2 |
1.6 |
22 |
8.8 |
0.007 |
Pre-eclampsia |
10 |
7.9 |
19 |
7.6 |
0.916 |
Transversely contracted pelvis |
0 |
0.0 |
13 |
5.2 |
0.116 |
TPB |
6 |
4.7 |
8 |
3.2 |
0.533 |
Eclampsia |
1 |
0.8 |
8 |
3.2 |
0.148 |
IUGR |
5 |
3.9 |
4 |
1.6 |
0.158 |
Placenta previa |
0 |
0.0 |
3 |
1.2 |
0.216 |
Urinary tract infection |
23 |
18.1 |
2 |
0.8 |
0.000 |
Malaria |
34 |
26.8 |
1 |
0.4 |
0.000 |
Abruptio placenta |
0 |
0.0 |
1 |
0.4 |
0.365 |
Pulmonary Infection |
3 |
2.4 |
0 |
0.0 |
0.476 |
Salmonellosis infection |
1 |
0.8 |
0 |
0.0 |
0.172 |
Moderate anemia |
63 |
49.5 |
10 |
3.9 |
0.000 |
Severe anemia |
29 |
22.8 |
5 |
2.0 |
0.000 |
Pregnancy outcome in women with sickle cell disease and in women without sickle cell disease
The average gestational age at delivery in sickle cell women was 36.04 WA ± 2.04 with the extremes of 27 WA and 40 WA. In non-sickle cell women, it was on average 37.48 WA ± 4.20 with the extremes of 22 WA and 41 WA. This difference between the two groups was statistically significant (p = 0.000).
Delivery was premature in 61.9% of pregnant women with sickle cell disease compared to 18.5% in pregnant women without sickle cell disease. This difference between the two groups was also statistically significant with a p-value equal to 0.000. The main route of delivery among sickle cell women was cesarean section (94.4%) while it was vaginal delivery (50.4%) among non-sickle cell pregnant women. It was prophylactic in 83.2% of pregnant women with sickle cell disease compared to 38.9% in those without sickle cell disease (Table 2).
Table 2. Distribution of sickle cell and non-sickle cell pregnant women according to the modalities of delivery at CHUD-B/A from 2019 to 2023.
|
Type of patient |
p-value |
With SCD |
Without SCD |
N |
% |
n |
% |
|
Term at delivery (WA) |
|
|
|
|
0.000 |
<37 |
78 |
61.9 |
47 |
18.5 |
|
≥37 |
48 |
38.1 |
207 |
81.5 |
|
Route of delivery |
|
|
|
|
0.000 |
Caesarean section |
119 |
94.4 |
126 |
49.6 |
|
Vaginal |
7 |
5.6 |
128 |
50.4 |
|
Type of cesarean |
|
|
|
|
0.000 |
Planned cesarean section (Prophylactic) |
99 |
83.2 |
49 |
38.9 |
|
Urgent cesarean section |
20 |
16.8 |
77 |
61.1 |
|
Among pregnant women with sickle cell disease, 5 (4.0%) gave birth to a stillborn neonate compared to 6 (2.4%) among those without sickle cell disease. This difference between the two groups was statistically insignificant. Pregnancies resulted in preterm deliveries in 61.9% of cases in pregnant women with sickle cell disease compared to 18.5% in pregnant women without sickle cell disease. This difference was statistically significant with a p-value equal to 0.000 (Table 3).
Table 3. Distribution of sickle cell and non-sickle cell pregnant women according to pre-partum and peri-partum complications at CHUD-B/A from 2019 to 2023.
|
Type of patient |
p-value |
With SCD |
Without SCD |
N |
|
N |
|
Antepartum fetal death |
|
|
|
|
0.379 |
No |
121 |
96.0 |
248 |
97.6 |
|
Yes |
5 |
4.0 |
6 |
2.4 |
|
Preterm birth |
|
|
|
|
0.000 |
No |
48 |
38.1 |
207 |
81.5 |
|
Yes |
78 |
61.9 |
47 |
18.5 |
|
VOC (4.8%), severe anemia (39.7%), postpartum hemorrhage (PPH) (1.6%) and acute pulmonary edema (APE; 2.4%) were the main complications reported in pregnant women in the immediate postpartum period (Table 4).
In total, among sickle cell pregnant women, 3 (2.4%) of them died. The maternal mortality rate was 23.6‰ in pregnant women with sickle cell disease compared to 0‰ in pregnant women without sickle cell disease. There were 2 deaths after pregnancy and one during pregnancy at the end of 27 WA. The causes of death were: hemorrhagic shock, disseminated intravascular coagulation and acute pulmonary edema (APE).
Table 4. Distribution of sickle cell and non-sickle cell pregnant women according to postpartum complications at CHUD-B/A from 2019 to 2023.
|
Type of patient |
p-value |
With SCD |
Without SCD |
N |
|
N |
|
VOC |
6 |
4.8 |
0 |
0.0 |
0.001 |
Severe anemia |
50 |
39.7 |
7 |
2.8 |
0.000 |
PPH |
2 |
1.6 |
1 |
0.4 |
0.223 |
APE |
3 |
2.4 |
0 |
0.0 |
0.014 |
Anemia (Mild/Moderate) |
0 |
0.0 |
4 |
1.6 |
0.679 |
High blood pressure |
0 |
0.0 |
1 |
0.4 |
0.324 |
Severe preeclampsia |
1 |
0.8 |
0 |
0.0 |
0.247 |
Postpartum psychosis |
0 |
0.0 |
1 |
0.4 |
0.578 |
Characteristics relating to neonates in the 2 groups of pregnant women
In total, there were 396 neonates, i.e. 135 for pregnant women with sickle cell disease and 261 for pregnant women without sickle cell disease. Low birth weight (weight < 2500 g) and birth length below the normal (50 cm) were significantly more observed in neonates born of sickle cell mothers compared to those born of non-sickle cell mothers with p-values of 0.002 and 0.000, respectively (Table 5).
Table 5. Distribution of sickle cell and non-sickle cell pregnant women according to the anthropometric and morphological characteristics of neonates at CHUD-B/A from 2019 to 2023.
|
Type of patient |
p-value |
With SCD |
Without SCD |
N |
|
N |
|
Condition of the neonate at birth |
|
|
|
|
0.361 |
Normal |
114 |
84.4 |
223 |
85.4 |
|
Neonate with respiratory distress |
16 |
11.8 |
32 |
12.3 |
|
Stillborn neonates |
5 |
3.7 |
6 |
2.3 |
|
Weight |
|
|
|
|
0.002 |
<2500 |
53 |
39.3 |
54 |
20.7 |
|
2500 - 3800 |
82 |
60.7 |
198 |
75.9 |
|
>3800 |
0 |
0.0 |
9 |
3.4 |
|
Length |
|
|
|
|
0.000 |
<50 cm |
117 |
91.4 |
177 |
70.8 |
|
≥50 cm |
11 |
8.6 |
73 |
29.2 |
|
Apgar at the 5th minute |
|
|
|
|
0.248 |
<7 |
4 |
3.1 |
7 |
2.8 |
|
≥7 |
124 |
96.9 |
243 |
97.2 |
|
Relationship between gestational age and birth weight |
|
|
|
|
0.001 |
Hypotrophy |
43 |
31.9 |
49 |
18.8 |
|
Normal growth |
90 |
66.7 |
191 |
73.2 |
|
Macrosomia |
2 |
1.5 |
21 |
8.0 |
|
Resuscitation |
|
|
|
|
0.907 |
Yes |
15 |
11.3 |
28 |
10.7 |
|
No |
120 |
88.9 |
233 |
89.3 |
|
In total, 120 (88.9%) neonates of pregnant women with sickle cell disease were transferred to the neonatology unit compared to 143 (54.8%) for those without sickle cell disease. The difference was statistically significant with a p-value equal to 0.000. In both cases the predominant reason for transfer was the delivery by cesarean section (70.8% vs 58.0%). In pregnant women with sickle cell disease, other more frequent reasons for transfer were low birth weight, prematurity and immediate neonatal distress.
The neonatal pathologies identified in neonates of pregnant women with and without sickle cell disease were mainly neonatal bacterial infection (20.0% vs 17.2%), hypotrophy (17.0% vs 5.7%), prematurity (14.8% vs 7.3%) with a significant difference. Early neonatal mortality was higher in neonates born of mothers with sickle cell disease, compared to those born of mothers without sickle cell disease, but the difference was not statistically significant (Table 6).
Table 6. Distribution of sickle cell and non-sickle cell pregnant women according to information relating to the transfer of neonates to neonatology at CHUD-B/A from 2019 to 2023.
|
Patient type |
p-value |
With SCD |
Without SCD |
N |
|
N |
|
Transfer to the neonatology unit |
|
|
|
|
0.000 |
No |
15 |
11.1 |
118 |
45.2 |
|
Yes |
120 |
88.9 |
143 |
54.8 |
|
Neonatal pathology |
|
|
|
|
|
Low birth weight |
53 |
39.3 |
54 |
20.7 |
0.000 |
Neonatal bacterial infection |
27 |
20.0 |
45 |
17.2 |
0.003 |
Hypotrophy |
23 |
17.0 |
15 |
5.7 |
0.000 |
Prematurity |
21 |
15.6 |
20 |
7.7 |
0.605 |
Perinatal asphyxia |
9 |
6.7 |
17 |
6.5 |
0.962 |
Neonatal jaundice |
6 |
4.4 |
3 |
1.1 |
0.386 |
Respiratory distress |
5 |
3.7 |
14 |
5.4 |
0.074 |
Anemia |
2 |
1.5 |
2 |
0.8 |
0.633 |
Hypoglycemia |
1 |
0.7 |
4 |
1.5 |
0.198 |
Malaria |
1 |
0.7 |
1 |
0.4 |
0.199 |
Evolution of neonates |
|
|
|
|
0.218 |
Living neonates |
132 |
97.8 |
259 |
99.2 |
|
Deceased neonates |
3 |
2.2 |
2 |
0.8 |
|
In terms of perinatal deaths, pregnant women with sickle cell disease had 5 intrauterine fetal deaths and 3 early neonatal deaths, i.e. 8 perinatal deaths out of 140 total births, i.e. a perinatal mortality rate of 57.14‰. The stillbirth rate was 35.71‰ and that of early neonatal mortality was 21.4‰. On the other hand, pregnant women without sickle cell disease had 6 intrauterine fetal deaths and 2 early neonatal deaths, i.e. 8 perinatal deaths out of 267 total births, i.e. a perinatal mortality rate of 30‰. The stillbirth rate was 22.5‰ and that of early neonatal mortality was 7.5‰.
3. Discussion
The frequency of sickle cell disease among pregnant women admitted to CHUD-B/A during the period was 1.36%. This frequency is similar to that reported by Agbeille et al. in the same department in 2019 [3]. On the other hand, Nwafor et al. [4] in 2019 in Nigeria and Nkwabong et al. [7] in 2020 in Cameroon found lower frequencies of 0.69% and 0.1%, respectively. This difference could be explained in part by the variability of the study population, but also by the variability in the prevalence of sickle cell disease depending on the regions of the world. The average age of the pregnant women was 26.77 years ± 5.03. This result is similar to 27.5 and 27 years reported by Nkwabong et al. [7] in Cameroon in 2020 and Galiba et al. [8] in Congo Brazzaville in 2020, respectively. The most represented age group was 25 to 30 years old (37%). Women of this age group are young, sexually active and capable of procreation.
Regarding specific complications, vaso-occlusive crisis was the most common (26%). This result is similar to that of Marielle et al. [9] in Gabon in 2022 who reported 27.3% of vaso-occlusive crisis. Dangbemey et al. [10] in Benin in 2018 reported in their study that the proportion of vaso-occlusive crises was 19.5%. This could be explained by the irregularity of follow-up of pregnant women.
In terms of non-specific complications, they were dominated by severe anemia (22.8%), malaria (16.5%), urinary tract infection (17.3%), gestational hypertension (14.2%). These complications were more frequent in pregnant women with sickle cell disease. Pregnant women with sickle cell disease were more likely to suffer from anemia (72.4%) than those without sickle cell disease (5.9%). This result was comparable to that of Haseeb et al. [11] in Saudi Arabia who reported 89.4% and 11.6% in sickle cell and non-sickle cell pregnant women, respectively. Anemia was found in 83 (65.3%) pregnant women with sickle cell disease. Among these 83 pregnant women with sickle cell disease, 42.5% had moderate anemia and 22.8% had severe anemia. Dangbemey et al. [10] reported 19.2% in Benin in 2020. Pregnancy is a factor that aggravates anemia in women with sickle cell disease. This anemia is the result of several factors including deficiency and infectious causes (bacterial infections and malaria). Urinary tract infection was more significant in pregnant women with sickle cell disease than in those without sickle cell disease (p-value < 0.001 in both cases). Haseeb et al. [11] in Saudi Arabia in 2019 and Babah et al. [12] in Nigeria in 2019, reported a statistically higher urinary tract infection in pregnant women with sickle cell disease compared to those without sickle cell disease (p-value of 0.001). Nkwabong et al. [7] in Cameroon in 2020, reported a higher frequency of urinary tract infection in pregnant women with sickle cell disease compared to those without sickle cell disease but the difference was not significant (p-value equal to 0.106). Bacterial infections are more common in women with sickle cell disease. They are the consequence of early functional asplenia with greater vulnerability to infections linked to encapsulated germs. But other factors have been identified as predisposing to bacterial infections, namely: neutrophil dysfunction, impaired cell-mediated immunity, impaired phagocytosis and the presence of ischemia, which constitute an environmental conducive to bacterial proliferation [13]. In our pregnant women, other factors may be associated with it, namely: the irregularity of pregnancy follow-up which does not make it possible to detect and treat these infections early. Hence the need to emphasize the education of patients and health care providers on pregnancy-related complications, the management of pregnancies, the benefits of early antenatal care according to protocol provided by a multidisciplinary team [14] [15].
Maternal death was observed in 3 pregnant women, including one during pregnancy and two after childbirth, bringing the maternal death rate to 2.4%. This rate was close to those reported by Dangbemey et al. [10] in Benin in 2020 and Oppong et al. [16] in Ghana which were 1.3% and 1.3%, respectively. This rate is lower than 11.4% and 6.2% reported by Galiba et al. [8] in Congo in 2020 and Faye et al. [17] in Senegal in 2018, respectively. Nwafor et al. [4] in Nigeria in 2019 reported 0% of maternal deaths. This difference could be explained by the quality of sickle cell disease management. In our study, the majority of pregnant women had a poor follow-up and developed severe complications during pregnancy and peripartum period. This suggests that the mainstay of antenatal care should include the follow-up and prevention of general and specific complications of sickle cell disease [18]. Indeed, it has been shown that improving antenatal care specific to pregnant women with sickle cell disease considerably reduces the maternal mortality rate which can be comparable to that among pregnant women without sickle cell disease [15].
4. Conclusion
Pregnancy among women with sickle cell disease is a clinical association. It remains common at the Regional Teaching Hospital of Borgou and Alibori. The course of pregnancy in pregnant women with sickle cell disease is often marked by multiple maternal and perinatal complications. Better follow-up of pregnancy, especially by specialized care centers, could improve the prognosis of pregnancy in this category of pregnant women.