Awareness and Acceptability of Prenatal Diagnosis of Sickle Cell Disease among Mothers of Affected Children in a Northern Nigerian Teaching Hospital

Version Changes

Revised. Amendments from Version 2

The revised manuscript has been substantially strengthened in response to the reviewers’ comments. Key findings are now more clearly presented, notably the high acceptability of prenatal diagnosis (PND) for sickle cell disease (93.3%) following the provision of information. Importantly, the manuscript now clarifies that among women who declined PND, religious beliefs rather than cost were the predominant reason, accounting for nearly half (45%) of non-acceptance. The discussion has been expanded to better contextualize these findings, including a more detailed examination of the influence of religious leaders in premarital counselling and their potential role in shaping informed reproductive decisions. In addition, the importance of health education targeted at younger populations as a long-term strategy for sickle cell disease control has been explicitly addressed. Several methodological and presentation-related improvements were also made. Errors in Table 1 were corrected, haemoglobin was removed from Table 2, and percentages were added to Table 4 to improve clarity. The method used for genotype assessment (alkaline electrophoresis) has now been clearly stated in the study setting within the methods section. Minor editorial revisions were undertaken throughout the manuscript to enhance readability and consistency. Further clarifications were provided in response to specific comments. The discussion on the role of cell-free DNA testing in prenatal diagnosis has been addressed. It has also been clarified that pregnancy status and maternal genotype were not assessed during data collection. The awareness level cited from Olatunya’s study was corrected to 25%. Lastly, the data collection process has been clarified, noting that questionnaires were interviewer-administered by two trained research assistants, and that participants unaware of PND for sickle cell disease were verbally informed about its availability and methods prior to assessing acceptability.

Abstract

Background

Nigeria has the highest global prevalence of sickle cell disease (SCD), necessitating effective preventive measures to control the disease. Prenatal diagnosis (PND) is a key early intervention for SCD, yet there is a shortage of studies in Northern Nigeria focusing on mothers of children with SCD. These mothers not only carry the burden of the disease but also face the risk of having more affected children, making them vital stakeholders in managing and controlling SCD. This study assessed the awareness and acceptability of prenatal diagnosis PND for SCD among mothers of children with the disease.

Methods

A cross-sectional study was conducted involving 297 mothers of children with SCD attending the Paediatric Haematology clinic at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Data were collected via an interviewer-administered questionnaire addressing the characteristics of the children and mothers, as well as their awareness, attitudes, and acceptability of PND. SPSS version 23 was used for data analysis, with a p-value < 0.05 considered statistically significant.

Results

Most participants (90.9%) were of Hausa ethnicity and 97.0% were of Islamic faith. A majority (77.8%) had less than tertiary education, and 57.9% lacked personal income. Nearly 41% had more than one child affected by SCD, and about one-fifth had lost a child to SCD complications. Only 22.2% of mothers had heard of PND, mostly from healthcare workers, and just 0.3% had undergone the procedure. After receiving information about PND, 93.3% were willing to accept it, though 45% of those who declined cited religious beliefs. Factors associated with PND acceptance included the mother's education and the child’s SCD severity.

Conclusion

Awareness of PND among at-risk mothers is low, yet most expressed willingness to accept it. Educational level and disease severity were associated with PND acceptability.

Plain language summary

Nigeria has the highest number of people with sickle cell disease (SCD) in the world. To help prevent more children from being born with the disease, prenatal diagnosis (PND) allows parents to know whether their baby will have SCD before birth. However, there is little research in Northern Nigeria focusing on mothers who already have children with SCD. These mothers carry the heavy burden of caring for sick children and face the possibility of having more children with the disease. Understanding how much these mothers know about PND and whether they would be willing to use it is important for controlling the spread of SCD. In this study, 297 mothers of children with SCD attending a hospital in Zaria, Nigeria, were surveyed. The mothers answered questions about their children, personal background, and knowledge of and willingness to accept PND. The data were analyzed to identify factors that influenced awareness and acceptability of PND. The majority of the mothers were Hausa and Muslim, and most had low levels of education. Over half of the mothers had no personal income. Nearly 41% of the mothers had more than one child with SCD, and about 20% had lost a child due to the disease. Only 22.2% of the mothers had heard of PND, mostly from healthcare workers, and just 0.3% had undergone the procedure. After learning more about PND, 93.3% of the mothers said they would be willing to use it. However, religious belief was the main reason for refusal among those who declined. Mothers with higher education levels and those whose children had more severe disease manifestation were more likely to accept PND. In conclusion, awareness of PND among these mothers is low, but most are open to it once informed. Educational efforts could improve acceptance of PND in Northern Nigeria.

Introduction

Sickle cell disease (SCD) is the most common hemoglobinopathy in sub-Saharan Africa (SSA) with Nigeria having the highest prevalence globally ^{1, 2} . The World Health Organisation (WHO) has identified SCD as a public health burden due to its high morbidity and mortality rates. In SSA, most affected children die before their fifth birthday, and survivors face recurrent episodes of anemia, blood transfusions, crises, and repeated hospital admissions. These not only cause physical ill-health but also lead to significant psychosocial trauma for affected individuals and their families, creating a substantial socio-economic burden on families, society, and the country ³ . Therefore, preventing SCD is essential to reduce its overall burden.

Early diagnosis of SCD is a key strategy in controlling the disease, as it allows for the timely implementation of appropriate and acceptable measures. Screening for SCD can occur at various stages of life, with prenatal diagnosis (PND) being one of the earliest available options. PND is performed during early pregnancy for couples at risk of having children with SCD. This diagnosis can be conducted using invasive tests, such as chorionic villus sampling or amniocentesis, and more recently, a non-invasive technique has been developed. The non-invasive prenatal test screens for fetal SCD using cell-free fetal DNA from maternal plasma, eliminating the risk of miscarriage associated with invasive tests ³ . This method also allows for earlier screening than conventional invasive tests. A recent systematic review indicates that non-invasive prenatal testing (NIPT) has strong potential as a dependable screening tool for identifying fetuses at risk of SCD; however, additional validation studies are needed to establish its diagnostic accuracy and clinical usefulness ⁴ .

There is a scarcity of centres offering PND in Nigeria, and its acceptability is often influenced by religious beliefs ⁵ . The benefits of PND include early detection of abnormalities in the fetus, allowing a couple time to prepare psychologically, socially, and financially for the birth of an affected child if they choose to continue the pregnancy. It also provides the option to terminate the pregnancy if the birth of an affected child is not desired, in situations where pregnancy termination is acceptable and permissible. Additionally, PND can relieve anxiety early in pregnancy if the disease is excluded.

Although some studies have been conducted on the knowledge and acceptability of PND of SCD in the general population, there is a lack of research in Northern Nigeria focusing on mothers of children with SCD. These mothers are already carrying the burden of the disease, are at risk of having another affected child, and are important stakeholders in SCD control. This study aims to assess the awareness and acceptability of PND of SCD among mothers of children with SCD.

Methods

Study setting

The study was conducted in the Paediatric Haematology clinic of Ahmadu Bello University Teaching Hospital, Zaria, which operates weekly on Wednesdays. The clinic sees an average of 50 children with SCD each week. The diagnosis of haemoglobin genotype in the hospital is done by alkaline electrophoresis.

Study design

This was a cross-sectional descriptive study.

Study population

The study population included mothers of children with SCD who were attending the clinic.

Inclusion criteria

All consenting mothers of at least one child living with sickle cell disease were included in the study.

Exclusion criteria

Exclusion criteria were menopausal mothers, mothers who had undergone bilateral tubal ligation, and mothers whose current spouse had an Hb genotype of AA.

Sample size determination

Using a prevalence of awareness of 0.25% among mothers of affected children as reported by Olatunya ⁶ , where n = sample size; Z = standard normal variate (1.96 at P<0.05); p = percentage of awareness of prenatal diagnosis (25%); q = 1-p (0.75), d = absolute precision (0.05), a minimum sample size of 288 was obtained. However, 297 women were recruited for the study.

Sampling technique

A non-probability sampling method was used to sequentially recruit eligible mothers of affected children from the clinic as they presented to access care until the desired sample size was achieved.

Study protocol

Every eligible participant completed a structured interviewer-administered questionnaire, after obtaining informed verbal consent, to gather data on socio-demographic characteristics, awareness, attitude, and acceptability of prenatal diagnosis for SCD. None of the eligible participants declined participation. The data collected was pseudo-anonymized. Recruitment took place from March to August 2023.

Data analysis

Data were analysed using the Statistical Package for Social Sciences (IBM SPSS statistics) version 23 ⁶ . The level of significance was set at <0.05. Frequencies and percentages were used to describe categorical data, and Chi-square/Fisher's exact test was used to test for associations between variables.

Ethics and consent

Ethical approval (ABUTHZ/HREC/H32/2022) was obtained from the Health Research Ethics Committee of ABUTH, Zaria, on 14 September 2022. Participants were provided with adequate information, and informed verbal consent was obtained from all the study participants before the questionnaires were administered. Verbal consent was used because it has been established in a national document that Kaduna state (where the study was conducted) has a low literacy level, with only 18% of the female population reported to have attained secondary or higher education (National Health Demographic Survey, 2018). The study also posed a no-minimal risk to the participants and the information collected was de-identified. The scope of the study and process involved was discussed with each participant. The participant was allowed the opportunity to ask questions and her concerns addressed if any before giving consent. The questionnaires were de-identified, and confidentiality was strictly maintained. Collected hard copy data was securely stored, and only the principal investigator had access to the input data on a computer.

Results

A total of 297 mothers of children with SCD were recruited. The majority of the mothers (90.9%) were of Hausa ethnicity, 97.0% were of Islamic faith, 77.8% had below tertiary education, and 57.9% had no source of personal income. About one-third of the mothers were grandmultiparous women (≥5 deliveries). Additionally, 40.7% had more than one child affected by SCD, and about one-fifth had experienced the loss of at least one child due to SCD-related complications. Further details are provided in Table 1.

Table 1. Socio-demographic characteristics of mothers of children with SCD.

Characteristic	Frequency (%)	Characteristic	Frequency (%)
Tribe		Religion
Hausa	270 (90.9)	Islam	288 (97,0)
Non-Hausa	27 (9.1)	Christianity	9 (3.0)
Educational level		Parity
Below tertiary	231 (77.8)	<5	186 (62.6)
Tertiary *	66 (22.2)	≥5	111 (37.4)
Residence		No. of children with SCD
Rural	79 (26.6)	1	176 (59.3)
Semi-urban/urban	218 (73.4)	≥1	121 (40.7)
Personal source of income		No. of sickle cell related deaths
Yes	125 (42.1)	0	235 (79.1)
No	172 (57.9)	≥1	62 (20.9)

*Tertiary: additional education beyond secondary level such as diplomas, degrees, postgraduate

Two-thirds of the affected children were aged five years or younger. The predominant hemoglobin genotype among the children was Hb SS (99%). Approximately half of the children experienced at least one crisis per month. In the past year, 55.2% of the children were hospitalized, and 44.4% received blood transfusions due to SCD-related complications. Detailed characteristics of the affected children attending the SCD clinic are provided in Table 2.

Table 2. Characteristics of the affected children attending the SCD clinic.

Characteristic	Frequency (%)
Age (years)
≤5	197 (66.3)
>5	100 (33.7)
Genotype
SS	294 (99.0)
SC	3 (1.0)
Average crisis per month
0	146 (49.2)
≥1	151 (50.8)
SCD-related blood transfusion in the last one year
0	165 (55.6)
≥1	132 (44.4)
SCD-related hospital admission in the last one year
0	133 (44.8)
≥1	164 (55.2)

Only 22.2% of the mothers (66 out of 297) had ever heard of PND for SCD. The most common source of information about PND was healthcare workers, while the least common source was electronic media. This is illustrated in Figure 1.

Figure 1. Sources of information about PND for SCD among mothers of affected children.

The colours represent the different sources of information about PND.

The majority of the mothers (44 out of 66) were unaware of the methods that can be used for PND. Among those who were aware, chorionic villus sampling or amniocentesis was the most commonly known method (14 out of 66). Only 13.6% (9 out of 66) of the mothers knew more than one method of PND. These findings are depicted in Figure 2.

Figure 2. Awareness of PND methods among mothers of children with SCD.

The bars represent the methods of SCD PND known to the participants.

Only one mother (0.3%) had ever undergone a form of PND of SCD. However, when informed about PND of SCD, 93.3% of the mothers expressed willingness to accept the test. Among those who were not willing to accept PND, 45% were willing to accept the fate of having another child with SCD. These findings are detailed in Table 3.

Table 3. Acceptability of PND for SCD among mothers.

Variable	Frequency (%) n=297
Ever had PND for SCD
Yes	1 (0.3)
No	298 (99.7)
Willingness to accept PND in the future	n=297
Yes	277 (93.3)
No	20 (6.7)
Reasons for unwillingness to accept PND in the future	n=20
I will accept my fate	9 (45.0)
No reason stated	11 (55.0)

Mother’s educational level, having a child experiencing at least one crisis per month, and receiving at least one blood transfusion or hospital admission in the past year were significantly associated with willingness to accept PND for SCD (p<0.05). These associations are presented in Table 4.

Table 4. Factors associated with the willingness to accept PND for SCD in future pregnancies.

	Frequency (%) n=297
Factor	Will accept PND	Will not accept PND	p-value
Educational level
Tertiary	57 (19.1)	9 (3.03)	0.011
Below tertiary	220 (74.1)	11 (3.7)
Personal source of income
Yes	116 (39.1)	9 (3.0)	0.785
No	161 (54.2)	11 (3.7)
Place of residence
Semi-urban/urban	202 (68.0)	16 (5.4)	0.489
Rural	75 (25.3)	4 (1.3)
No. of SCD-related death
≥1	57 (19.1)	5 (1.7)	0.638
0	220 (74.1)	15 (5.1)
Average crisis per month
≥1	147 (49.5)	4 (1.3)	0.005
0	130 (43.8)	16 (5.4)
SCD-related blood transfusion in the last one year
≥1	128 (43.1)	4 (1.3)	0.034
0	149 (50.2)	16 (5.4)
SCD-related hospital admission in the last one year
≥1	161 (54.2)	3 (1.0)	0.000
0	116 (39.1)	17 (5.7)
No. of children affected with SCD
≥2	167 (56.2)	9 (3.0)	0.158
1	110 (37.0)	11 (3.7)

Discussion

The global number of people with SCD has increased by 41.4% over the past 21 years ⁷ . The birth prevalence of SCD among children under one-year-old is reported to be highest in Africa, ranging from 643 to 2800 per 100,000, with particularly high mortality rates ⁸ . This highlights the urgent need for effective SCD control measures in SSA to reduce associated morbidity and mortality. PND is one of the reproductive options available to couples at high risk of transmitting a serious genetic disorder. Awareness and utilization of PND have increased in developed countries, where it is routinely offered as part of informed reproductive choices, but remains low in Africa, which carries the highest burden of the disease ⁹ .

This study found a low level of awareness of PND for SCD, which aligns with findings by Olatunya et al. in Southwestern Nigeria ¹⁰ . Similarly, Munung et al. in a multi-country study of people directly affected by SCD, reported a low level of awareness of PND ¹¹ . This low level of awareness mirrors the general awareness of prenatal diagnosis for other genetic conditions in various study populations, such as pregnant women ^{12– 14} . In northern Nigeria, Aliyu et al. reported a similar awareness level of PND for SCD among pregnant women ¹⁵ . The widespread poor awareness of PND for genetic disorders could be attributed to a lack of facilities and expertise for PND in Nigeria and the reluctance of some healthcare workers to recommend PND for SCD. A study among physicians found that nearly two-thirds would not recommend PND for at-risk couples ¹⁰ . This also highlights the low uptake of PND for SCD in this study, with only one mother having undergone PND in a previous pregnancy, as reported in a similar study in Nigeria ¹⁴ . In contrast, Okechukwu et al. found higher awareness of PND (52.2%) among parents of SCD children in South-South Nigeria ¹⁶ .

In this study, the internet and social media were not major sources of information about PND for SCD. In the digital era, this emphasizes the need for organisations responsible for SCD control to utilise these media to disseminate accurate and easily understandable information.

Following information on PND for SCD provided to participants in this study, the majority expressed a willingness to accept PND, consistent with reports by Ampumah et al. from Ghana and Wonkam et al. from Cameroon ^{17, 18} . However, Olatunya et al. and Okechukwu reported lower acceptability rates in similar populations ¹⁶ . This could be due to differences in the intrinsic characteristics of the study populations. In the study by Olatunya, 97% of participants had only one affected child, whereas more than half of the mothers in this study had more than one affected child. Additionally, mothers in this study had experienced SCD-related deaths five times more frequently than participants in Okechukwu’s study. Caring for a person with SCD carries a significant psychological, financial, and physical burden ¹⁹ . This burden is even greater when more than one child in a family is affected by SCD, which may influence mothers' attitudes toward the acceptability of PND for SCD. Aliyu et al. reported a lower level of acceptability among pregnant women, which may be attributed to differences in study populations, as their study involved a general antenatal population, unlike the more selectively recruited participants in the present study ¹⁵ .

In this study, nearly half of the mothers who were unwilling to accept PND cited a willingness to accept the risk of having another affected child. Acceptance of one’s fate is closely associated with religious belief, similar to findings from southern Nigeria ¹⁶ . Religion is a strong factor in the decision-making process for prenatal screening ²⁰ . This study found that severe manifestations of the disease evident by frequent crises, blood transfusions, and hospital admissions were associated with willingness to accept PND. The psychosocial burden faced by these mothers of affected children does not exist in other studied populations, such as healthcare providers or students ²¹ . Cultural, religious, and personal concerns about pregnancy termination are factors associated with willingness to accept PND for SCD ^{11, 20} . Ampumah et al. in Ghana reported that parents of children living with SCD were more likely to use PND results to prepare for the birth of the child, and deciding to accept PND did not necessarily mean using that information to terminate the pregnancy ¹⁷ . Munung et al. in Ghana found a lower preference for PND as a SCD control measure largely due to its complex decision-making process and higher risk of stigmatization which are influenced by religious and cultural aspects attached to the termination of an affected pregnancy that can follow a PND ¹¹ . In a resource-poor country where the resources to establish widespread PND is lacking; a populace whom cultural and religious beliefs influence their decision making; a restrictive abortion law and high burden of SCD-related morbidity and mortality, there is need to strengthen other less expensive control measures in the countries like premating/premarital counseling and testing and newborn screening. In the Nigerian setting, awareness and acceptance of premarital screening for SCD are already relatively high ²² , and studies have shown that many African individuals hold positive attitudes toward genetic counselling ²³ . Evidence from a multi-African country study by Munung et al. further suggests that adolescents may be an ideal target group for early sickle cell trait screening, given their openness to receiving genetic information before marriage decisions are made ¹¹ . This indicates a valuable opportunity to expand low-cost control measures. In contexts where religious leaders play a central role in guiding social and marital decisions, their involvement could significantly enhance the uptake and acceptability of other control measures like premarital screening. Engaging community faith structures—for example, offering voluntary carrier testing through local mosques or churches—may be culturally appropriate and effective. Religious leaders often hold strong influence and have been shown to express supportive attitudes toward premarital SCD screening, and they could play a constructive role in communicating the health implications of two carriers marrying ²⁴ . A study in northwestern Nigeria reported that providing health education to Islamic clerics increased their knowledge on SCD and willingness to advocate premarital counselling to intending couples ²⁵ . Cell-free fetal DNA testing in maternal serum is currently unavailable in Kaduna, and only a few centres offer the service nationwide, at prohibitively high costs.

Educational level was the only socio-demographic variable of mothers associated with willingness to accept PND, similar to findings by Mattei et al. in a recent systematic review ²⁶ . Other studies have also reported that educational level is generally associated with willingness to accept PND, not just for SCD ^{27, 28} .

This study derives its strengths from the use of a large sample size; use of a relevant target population of women with a strong stake in control measures of SCD like PND; provides valuable insights into public health strategies and interventions in the control of SCD in a country with the highest burden of SCD and thus could inform future research and policy. The high level of acceptability observed is likely to enhance the uptake of this control measure. Meaningful involvement of religious leaders who have received accurate and comprehensive education on sickle cell disease within the national control programme is also likely to improve community perceptions and attitudes toward the full range of SCD control strategies.

Limitations of this study include the use of a convenience sampling method as it does not randomly select mothers from the target population; reliance on self-reported data where the respondents may not truly reveal their beliefs and attitudes and being a single-centred study where the respondents were Muslims and of Hausa ethnicity which could limit diversity of perspectives represented in this study.

Conclusion

Only one-fifth of at-risk mothers were aware of PND as a control measure for SCD, and actual use of PND was very low. Most mothers expressed a willingness to accept PND and religious belief was the main reason for declining PND. Mother’s educational status and the severity of the child's disease were associated with a willingness to accept PND.

Funding Statement

This project has received funding from the European Union’s Horizon Europe research and innovation programme under the Marie Skłodowska-Curie grant agreement No [GA 824021 — ARISE — H2020-MSCA-ARISE-2018]. The authors declare that there was no financial grant directly involved in supporting this work."

Data availability statement

The data underlying this article are openly available in the Figshare repository under a CC BY 4.0. The dataset can be accessed via the following DOI 10.6084/m9.figshare.27195288 ⁶ .

Data are available under the terms of the CC BY 4.0