Periconceptional folic acid usage and its associated factors in eastern Sudan: A cross-sectional study

Abstract

Background:

Several countries poorly adhere to the World Health Organization’s recommendation of folic acid supplementation in the periconceptional period, especially in limited-resource settings.

Objective:

The objective of this study was to investigate the prevalence of and the factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital in eastern Sudan.

Study design:

This is a cross-sectional study.

Methods:

This study was conducted in eastern Sudan from April to September 2022. A total of 720 pregnant women in their first trimester were enrolled. The sociodemographic characteristics and clinical and obstetrical data of pregnant women in their first trimester were assessed using a face-to-face questionnaire. In addition, multivariate regression analysis was performed.

Results:

In this study, the median (interquartile range) of the age and gravidity of the enrolled women was 26.3 (24.14–29.52) years and 2 (1–4), respectively. Of these 720 women, 423 (58.8%) used folic acid during the periconceptional period, while 27 (3.7%) women used folic acid in the preconceptional period. None of the investigated factors (age, residence, education, employment, body mass index, or gravidity) were associated with periconceptional use of folic acid.

Conclusion:

The study revealed a low prevalence of folic acid usage in preconceptional period among pregnant women in eastern Sudan. Additional efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.

Introduction

Maternal folate deficiency in the periconceptional and early pregnancy period may lead to adverse maternal and perinatal outcomes, including neural tube defects (NTDs).^{1 –3} The World Health Organization (WHO) recommended pregnant women taking 0.4 mg/day of folic acid in the periconceptional period. ¹ However, higher doses (4–5 mg/day) are recommended for higher-risk groups such as those with periconceptional antiepileptic drug exposure, pre-gestational diabetes, pre-pregnancy obesity, or family history of NTDs.^4,5 The act of taking folic acid before conception and continuing until 12 weeks of gestation (periconceptional period) is associated with a lowered risk of NTDs, ⁶ congenital heart defects, ⁷ spontaneous abortion, stillbirth, ³ preterm birth,^2,8 and anemia. ⁸ In spite of this WHO recommendation and its documented benefits, the use of folic acid supplementation in the periconceptional period is still low in several countries, especially in countries with limited-resource settings.^{3,9 –11} Several factors—such as age, maternal education levels, occupation, parity, and unplanned pregnancy—determine the compliance and adherence of pregnant women to the WHO’s recommendations, that is, the early periconceptional taking of folic acid. ¹⁰ Many factors were reported by researchers that can lead to low folic acid supplementation in periconceptional period such as lack of knowing the importance for the fetal development, difficulty in getting folic acid, low socioeconomic status, and the culture background of the family.^{12 –14}

NTDs are a major health problem in Africa; this might be attributed to lack of adherence to the WHO’s recommendations regarding folic acid supplementation in the periconceptional period.^{9,11,15 –17} A recent meta-analysis included 20 studies consisting of 752,936 individuals showed a pooled prevalence of all NTDs per 10,000 births in eastern Africa was 33.30 (95% confidence interval (CI) = 21.58–51.34). ¹⁵ A systematic review and meta-analysis conducted by Toivonen et al. ¹¹ reported variable pooled prevalence estimates for preconception folic acid supplementation among different countries worldwide for which data were available, that is, the highest among countries within North America (32%–51%) and Europe (9%–78%) and the lowest in parts of Africa (0%). In Sudan, previous studies reported a lack of women taking folic acid during pregnancy, the late initiation of folic acid supplementation after conception, and low and irregular folic acid intake.^9,16,17 For example, Omer et al. ⁹ studied 103 newborns with NTDs, 68 (66%) of the studied mothers received folic acid during pregnancy with the current child, of those who received folic acid, 66 (97.1%) started folic acid after conception, 36 (54.5%) in the first trimester, and 39 (57.4%) had no regular intake of the folic acid. A lack of folic acid intake can lead to poor maternal and perinatal outcomes, including NTDs,^9,16,17 preterm births, ¹⁸ and anemia. ¹⁹

In Sudan, the existing studies which conducted in Khartoum, central Sudan, showed high prevalence of spina bifida and its complications.^9,16,17 For example, Omer et al. ⁹ in their hospital-based cross-sectional study, involved all newborns with any type of NTD admitted to the neonatal intensive care unit (NICU) in Khartoum, Sudan, out of the 36,785 delivered newborns during the study period, the prevalence of NTDs was 2.8 per 1000. Moreover, our previous published data including the study area showed high morbidity and mortality pattern of neonates admitted into NICU, ²⁰ low used of folic acid and poor antenatal care, ²¹ and high rate of various drugs usage during pregnancy including antiepileptic. ²² Although many countries have fortified folic acid in grain that showed effectiveness in reducing the occurrence of NTDs, further efforts are needed to establish such program in Sudan.^23,24 All these raised issues indicate NTDs are a public health problem in Sudan, and their causes’ needs to be explored. However, no published data exist on the use of folic acid supplements in the periconceptional period in Sudan. Such studies are needed to know the current situation and to advocate for the early usage of folic acid to prevent its complications. Thus, this study aimed to investigate the prevalence and factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital, eastern Sudan.

Methods

Study area and design

This cross-sectional study was conducted among pregnant women who presented for antenatal care in their first trimester at Gadarif Maternity Hospital, Gadarif, eastern Sudan, between April and September 2022. In this study, Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were strictly followed ²⁵ (Supplementary File 1).

Gadarif Maternity Hospital is the largest maternity hospital in Gadarif State; it provides maternity services for all women in eastern Sudan regardless of their residency (urban or rural) and pregnancy status (complicated or not complicated). About 8000 newborns per year were delivered at Gadarif Maternity Hospital eastern Sudan. Hence, the population recruited from the Gadarif Maternity Hospital represents the pregnant women in eastern Sudan. Gadarif State neighbors Ethiopia and is located in east Sudan, approximately 400 kilometers from the capital, Khartoum. It is one of the 18 states in Sudan with a total population of 2.5 million people. ²⁶ The capital of the state is Gadarif Town. Gadarif State is described as a multiethnic state; because it contains Sudanese tribes from all the various regions of Sudan. ²⁶

Study participants

During the study period, every pregnant woman in her first trimester who came to the hospital for antenatal care was approached by trained research assistants. All the study issues (i.e. the aims of the study and the ethical issues) were clearly explained to women who were confirmed by the research assistants to be eligible and pregnant.

Inclusion criteria

Any woman who attended Gadarif Maternity Hospital for antenatal care in her first trimester (the first 13 weeks of gestation), had a singleton pregnancy, provided voluntary informed written consent, was apparently healthy, and not known to be ill was eligible to participate in this study.

Exclusion criteria

Women who refused to sign the consent form for participation in the study, women not in their first trimester (14 weeks or more of gestation), women with pre-gestational chronic diseases such as diabetes mellitus and epilepsy, and severely ill women were excluded from the study.

Data collection

A questionnaire was used during face-to-face interviews to collect the data. The questionnaire was designed based on previous similar studies^3,8,10 (Supplementary File 2). The questionnaire included questions regarding sociodemographic information, such as maternal age in years, place of residence (rural or urban), maternal education (<secondary or ⩾secondary), and formal employment (housewives or employed). In addition, it sought to obtain clinical and obstetrical information, such as gravidity, and gestational age calculated in weeks (according to the last menstrual cycle and confirmed by ultrasound) and folic acid supplementation (before or/and during pregnancy), that is, folic acid usage starting before conception was defined as preconceptional folic acid user, folic acid usage in the first trimester was defined as postconceptional folic acid user, and folic acid usage starting before conception and/or in the first trimester was defined as periconceptional folic acid user. Three female research assistants were trained by the investigators to collect the data through face-to-face interviews.

Anthropometric measurements

The women’s weights were measured in kilograms (kg) via well-calibrated scales. To standardize the procedure before each measurement, the device was adjusted to zero. Each eligible woman was asked to stand with minimal movement, have their hands by their sides, and remove any shoes or excess clothing and belongings. After that, each woman’s height was measured in centimeters (later converted into meters, m). Each woman was asked to stand straight with her back against a wall and her feet together. Body mass index (BMI) was computed from weight and height as follows: the weight in kg was divided by the square of the height in m (kg/m²). ²⁷ Moreover, BMI was categorized based on the WHO classification that addresses obesity in early pregnancy as well as in the general population: underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), or obese (⩾ 30.0 kg/m²). ²⁷

Sample size calculation

An OpenEpi Menu was used to compute the desired sample size. ²⁸ A total sample size of 600 pregnant women in their first trimester was included in this study. This computation was based on a previous study conducted in central Sudan, ²⁹ as this is the first study that tackled folic acid supplementation in the periconceptional period, particularly in eastern Sudan. We assumed that 58.4% of these women used folic acid in their preconceptional and first trimester periods (ratio of usage: non-usage of folic acid = 1.5:1). ²⁹ Moreover, their study found that 40.4% and 32.2% of educated (<secondary level) and non-educated (⩾ secondary level) women used folic acid supplementation in the periconceptional period. ²⁹ This sample size was calculated to detect a difference of 5% at α = 0.05, with a power of 80%.

Statistical analysis

Data were entered in the computer using the IBM Statistical Package for the Social Sciences^® (SPSS^®) for Windows, version 22.0 (SPSS Inc., Armonk, New York, USA). The continuous data were evaluated for normality using the Shapiro–Wilk test and were found to be non-normally distributed (age, gravidity, parity, and BMI). The Mann–Whitney U-test was used for non-normally distributed data. The non-normally distributed data were expressed as the median (interquartile range, IQR). The chi-square test was used for categorical data, and the proportions were expressed as frequencies (%). Initially, univariate analysis was performed with the non-use of folic acid supplementation in the periconceptional period as the dependent variable and sociodemographic (age, residence, educational level, and occupation) characteristics and clinical and obstetrical characteristics (BMI, gravidity, and history of abortion) as independent variables. Furthermore, all the independent variables in the univariate analysis were entered in the multivariate analysis regardless of their significance to control for confounding variables. Adjusted odds ratios (AORs), 95% confidence intervals (CIs), coefficients, and standard errors were calculated as they were applied. A two-sided P-value of <0.05 was considered statistically significant.

Results

A total of 720 pregnant women in their first trimester were enrolled. The median (IQR) of the age and gravidity of the enrolled women was 26.3 (24.14–29.52) years and 2 (1–4), respectively. A total of 180 women (25.0%) were educated (⩾secondary level), and a few women 38 (5.3%) were formally employed. A total of 525 (72.9%) women were urban residents, while only 195 (27.1%) women were rural residents (Table 1).

Table 1.

Comparison of the sociodemographic and clinical factors between the use and the non-use of folic acid among pregnant women in eastern Sudan, 2022 (n = 720).

Variables		Total (n = 720)	Did not use folic acid (n = 297)	Used folic acid (n = 423)	P
Median (interquartile range)
Age (years)		24.0 (20.0–29.0)	23.0 (19.0–28.0)	25.0 (20.0–30.0)	0.033
Gravidity		2 (1–4)	2 (1–3)	2 (1–4)	0.027
Parity		1 (0–3)	1 (0–2)	1 (0–3)	0.084
Body mass index (kg/m2)		26.30 (24.14–29.52)	26.16 (23.63–29.48)	26.49 (24.30–29.52)	0.427
Frequency (proportions)
Residence	Urban	525 (72.9)	224 (75.4)	301 (71.2)	0.205
	Rural	195 (27.1)	73 (24.6)	122 (28.8)
Education level	⩾Secondary	180 (25.0)	71 (23.9)	109 (25.8)	0.570
	<Secondary	540 (75.0)	226 (76.1)	314 (74.2)
Formal employment	Housewives	682 (94.7)	284 (95.6)	398 (94.1)	0.365
	Employed	38 (5.3)	13 (4.4)	25 (5.9)
Body mass index groups	Underweight	11 (1.5)	3 (1.0)	8 (1.9)	0.176
	Normal weight	235 (32.6)	107 (36.0)	128 (30.3)
	Overweight	318 (44.2)	119 (40.1)	199 (47.0)
	Obese	156 (21.7)	68 (22.9)	88 (20.8)
History of abortion	No	613 (85.1)	255 (85.9)	358 (84.6)	0.649
	Yes	107 (14.9)	42 (14.1)	65 (15.4)

Of these 720, 423 (58.8%) used folic acid during the periconceptional period, and 297 (41.2%) did not. Of those who used folic acid 423, only 27 (3.7%) women used folic acid in the preconceptional period. Women who used folic acid in the periconceptional period were older compared to their counterparts, with a median (IQR) of 25.0 (20.0–23.0) versus 23.0 (19.0–28.0) years.

In adjusted logistic regression analysis, none of the factors (age, residence, education, employment, BMI, gravidity, and history of abortion) were found to be significantly associated with the non-use of folic acid in the periconceptional period. While age was associated with the non-use of folic acid in univariate analysis (unadjusted OR = 0.97, 95% CI = 0.94–0.99), it was not found to be associated in the multivariate analysis (Table 2).

Table 2.

Univariable and multivariable analyses of factors associated with the non-use of folic acid in periconceptional period among pregnant women in eastern Sudan, 2022.

Variables		Univariate analysis	Multivariate analysis
		Odds ratio (95% confidence interval)	Odds ratio (95% CI)	P
Age (years)		0.97 (0.94–0.99)	0.98 (0.94–1.01)	0.200
Gravidity		0.95 (0.89–1.01)	0.97 (0.89–1.06)	0.540
Body mass index (kg/m2)		1.01 (0.98–1.05)	1.03 (0.99–1.06)	0.084
Residence	Urban	Reference
	Rural	1.24 (0.88–1.74)	1.22 (0.82–1.83)	0.332
Education level	⩾Secondary	Reference
	<Secondary	1.11 (0.78–1.56)	1.00 (0.66–1.52)	0.993
Formal employment	Employed	Reference
	Housewives	1.37 (0.69–2.73)	1.17 (0.54–2.51)	0.695
History of abortion	Yes	Reference
	No	1.10 (0.72–1.68)	0.93 (0.59–1.46)	0.741

CI: confidence interval.

Age, gravidity, and body mass index were analyzed as continuous variables.

Of these 27 who used folic acid in the preconceptional period, 13 were primigravida, 12 were educated, 8 were formally employed, 12 were urban residents, 5 had a past history of abortion, and 11 were obese.

Discussion

The main findings of this study were that only 3.7% of pregnant women used folic acid in the preconceptional period and 58.5% during the periconceptional period. Our study demonstrates a low prevalence (3.7%) of using folic acid in the preconceptional period in eastern Sudan. These results are comparable to a previous study among 1000 pregnant women in Khartoum, central Sudan, which revealed that 3.2% of women used folic acid during the preconceptional period, while 55.2% used folic acid during the first trimester. ²⁹ In Ethiopia, a cross-sectional study that included 417 pregnant women showed that only 1.9% used folic acid in the preconceptional period and that 48.4% of women used folic acid during pregnancy. ³⁰

This folic acid usage prevalence in the preconceptional period (3.7%) was considerably lower than that reported in different countries, including Africa countries.^{31 –33} A cross-sectional study in Cameroon among 393 pregnant women 5.1% used folic acid in the preconceptional period. ³¹

A cross-sectional study of 660 pregnant women in Egypt reported that 124 (18.8%) used folic acid in the periconceptional period, with 58 (8.8%) using in the preconceptional period and 80 (12.1%) in the first trimester. ³⁴

It is clear that low usage of folic acid in the preconceptional period exists in Africa (less than 10%) compared to other countries such as Lebanon, ³⁵ the Netherlands, ³² and China. ³³ A cross-sectional study of 465 pregnant women in Lebanon showed that 125 (26.9%) used folic acid in the preconceptional period. ³⁵ A population-based cohort study in the Netherlands included 5975 pregnant women reported that 55.5% used folic acid during the preconceptional period. ³² Finally, a cross-sectional study in China that included 428 pregnant women showed that 46.3% used folic acid during the preconceptional period. ³³

Marked variations ranging from 0% to 98% in the prevalence of folic acid usage in the preconceptional period were reported among countries. ¹¹ For example, a systematic review and meta-analysis of 105 articles estimated an extremely low prevalence of folic acid during the preconceptional period in Africa (0%) compared to North America (32%–51%), Europe (9%–78%), Asia (21%–46%), the Middle East (4%–34%), and Australia/New Zealand (32%–39%). The estimated of 0% in Africa was based on two studies conducted in Nigeria and a single study conducted in Uganda. ¹¹

Researchers attributed the low prevalence of folic acid usage in the preconceptional period in Africa, including Sudan, to several factors, such as low maternal education,^11,29 poor knowledge on risks/benefits of folic acid usage, ²⁹ and lack of preconceptional counseling,^31,36 and late antenatal care initiation and, as a consequence, the late usage of folic acid.^17,29 For instance, in central Sudan, while a low prevalence of folic acid usage (3.5%) was found in women with low education and low knowledge about folic acid, a relatively high folic acid usage (8.3%) existed with women with high education (college-educated) and high knowledge of folic acid usage. ²⁹ This low prevalence of preconceptional folic acid usage could explain the poor maternal and perinatal outcomes, especially the high prevalence of NTDs among delivered Sudanese newborns (2.8/1000).^9,17

This study, however, showed low folic acid usage in the preconceptional period (27/720; 3.7%) and a relatively high (396/720; 55.0%) folic acid usage during the first trimester. This is similar to a previous study in central Sudan among 36,785 delivered newborns: 103 women had NTDs, of which 68 used folic acid, with 2 (2.9%) and 66 (97.1%) starting folic acid before and after conception, respectively. ⁹

Compared with other studies from different countries, the current periconceptional folic acid prevalence (58.5%) is higher than previously reported ones in Egypt (18.8%) ³⁴ and Cameroon (31.6%) ³¹ and lower than in the Republic of Ireland (97%) ³⁷ and China (95.2%). ² For example, in the Republic of Ireland, a cross-sectional observational study included only 856 pregnant women in their first trimester and found a suboptimal usage of folic acid both before and after conception, in spite of the high usage of folic acid in the periconceptional period (97%). ³⁷ Furthermore, the study identified a suboptimal usage of folic acid before conception, as only one in four women used folic acid for at least 12 weeks preconceptionally; as to women who only used folic acid postconceptional, almost two-thirds started after day 28 of their pregnancy, when the neural tube had already closed. ³⁷

This study showed no association between sociodemographic and obstetric factors and folic acid usage in the periconceptional period. In line with our results, our study in central Sudan showed that place of residence and maternal education were not associated with folic acid usage. ⁸ A previous cross-sectional study in Cameroon showed that age, maternal education level, and history of an unsuccessful pregnancy were not associated with folic acid usage in the periconceptional period. ³¹ Moreover, in Lebanon, maternal education level had no association with folic acid usage before and during pregnancy. ³⁵ Furthermore, this study showed that BMI and a history of abortion were not associated with folic acid usage in the periconceptional period; a study in China showed similar results. ³⁸

In contrast, other studies identified an association between the non-use of folic acid in the periconceptional period and older maternal age, low maternal education, and formal employment.^10,38 Although several studies reported an association between high maternal education and folic acid usage in periconceptional period, ¹⁰ others reported no association.^31,35 In our neighboring country, Ethiopia, higher maternal education did not result in increased folic acid usage. ³¹ In contrast, a multicenter study in Vietnam assessed folic acid usage among 2030 pregnant women and identified a link between high maternal education level and correct folic acid usage. ¹⁰ The lack of influence of maternal education on folic acid usage in the periconceptional period could be explained by many reasons, one of which may be the quality of education that positively influences health (using folic acid) rather than the number of years of schooling. ³⁹ It is worth mentioning that a poor education system exists in Africa, especially in girls’ schools. ⁴⁰

Regardless of maternal education level, all women of childbearing potential before conception should be encouraged to attend preconceptional counseling sessions managed by healthcare professionals. ⁴¹ Unfortunately, a systematic scoping review that included 39 articles from Sub-Saharan African countries revealed suboptimal usage of preconception care services, and folic acid preconception supplementation was the least-sought service compared with HIV testing. ³⁶ Facility-based and media-based campaigns can be a good approach to raising awareness about the importance and timely initiation of folic acid in the childbearing period.^13,34,41

This study has several strengths, of them, to the best of our knowledge, this is first study that addressed periconceptional folic acid usage, this study adds to the existing knowledge of folic acid usage in the periconceptional period in Sudan, ²⁹ and folic acid advocacy in the preconceptional period, ⁹ especially from an understudied region (eastern Sudan); the results of this study, especially the low prevalence of preconceptional supplementation, could be used by the policymakers in Sudan to take further actions such accelerating implementation of folic acid fortification programs in Sudan. However, this study has some limitations that must be mentioned. Due to the nature of this study as a cross-sectional study, it is difficult to correlate the effect of folic acid usage in the periconceptional period with maternal and perinatal outcomes. Thus, a longitudinal study should generate more information regarding the impacts of folic acid usage on maternal and perinatal outcomes (e.g. NTDs). In this study, the used questionnaire was not pre-tested/validated, and this is one of the limitations. Although our study had a large sample size, it does not provide nationally representative data on folic acid usage among pregnant Sudanese women, it studied one geographical region only (eastern Sudan). Even for eastern Sudan, the current sample size was not big enough for the prevalence rate of preconceptional supplementation which was 3.7%. However, this low prevalence in this study may encourage researchers to conduct further studies. Moreover, our study did not collect as much information about ethnicity as compared to other studies, ³² given that Gadarif State is a multiethnic society. ²⁶ Other factors that may lead to low folic acid supplementation in periconceptional period such as lack of knowing the importance for the fetal development, difficulty in getting folic acid, low socioeconomic status, and the culture background of the family^{12 –14} were not investigated. Furthermore, information about the correlation of folic acid usage with serum folic acid levels is limited, as several dietary sources can contain folic acid, and dietary habits such as fruit and vegetables intake ²⁹ are crucial and can be obtained in future research. Conducting further study to overcome the abovementioned limitations is desirable.

Conclusion

The study revealed a low prevalence of folic acid usage in the preconceptional period among pregnant women in eastern Sudan. More efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.