Regular Antenatal Attendance and Education Influence the Uptake of Intermittent Preventive Treatment of Malaria in Pregnancy: A Cross-Sectional Study at the University Hospital, Kumasi, Ghana

Background The World Health Organization (WHO) recommends the use of Insecticide Treated Bed-Nets and Intermittent Preventive Treatment (IPT) with Sulphadoxine-Pyrimethamine (SP) as interventions in curbing malaria during pregnancy. However, increasing evidence shows a gap in coverage where not all pregnant women receive the recommended SP dose. This study evaluated the factors influencing uptake of IPTp-SP among pregnant women in Kumasi, Ghana. Methodology This cross-sectional study was conducted among 280 pregnant women attending the Kwame Nkrumah University of Science and Technology Hospital in Kumasi, Ghana. Validated structured questionnaires were administered to obtain sociodemographic, medical/reproductive information, and IPTp-SP uptake among participants. Statistical analyses were performed using IBM SPSS 25.0 statistics. Results The mean age of respondents was 29.7±4.9 years. Of the 280 women interviewed, 74.6% attended the antenatal care (ANC) clinic at least four times with only 31.8% completing the recommended doses. Tertiary education [aOR=3.15, 95% CI (0.94 -10.97), and p=0.042] and ≥ 4 ANC visits [aOR=24.6, 95% CI (5.87-103.07), p<0.0001] had statistically significant higher odds of completing the recommended IPTp-SP dose. However, participants employed by the formal sector [aOR=0.28, 95% CI (0.09 - 0.79), p=0.016] and participants with more than four children [aOR=0.14, 95% CI (0.03 - 0.63), and p=0.011] had statistically significant lower odds of completing the recommended IPT dose. Conclusion ANC attendance is critical in IPTp uptake. The results emphasize the need for the Health Policy Makers in Kumasi to encourage pregnant women, especially women working in the formal sector and women having more than four children to patronize ANC attendance to ensure high coverage of the recommended IPTp dose.


Introduction
Pregnant women as well as the foetus are vulnerable to malaria infection [1], which has been associated with anaemia, maternal death, spontaneous abortions, low birth weight, and neonatal death [2,3]. While malaria is a preventable and treatable disease, it continues to remain the leading cause of outpatient department (OPD) attendance in Ghana [4,5]. It is still the most commonly reported disease, accounting for over 55.0% of all OPD attendance [5], 13.7% of admissions among pregnant women, and 3.4% of maternal deaths [6]. The first and second pregnancies are normally the most influenced. The prevalence of parasitaemia is prominent in the second and third trimesters and susceptibility to 2 Journal of Tropical Medicine clinical malaria may persist into the postpartum period [6].
The administration of Sulphadoxine-Pyrimethamine (SP) during ANC visits as recommended by the WHO is to ameliorate the effects of malaria in pregnancy [4,7]. ANC clinic attendance provides a planned programme for medical management of pregnant women whilst ensuring safe motherhood [8][9][10][11][12]. A cross-sectional study by Azizi et al. reports an association between the number of ANC visits and use of DOTs with the utilization of at least three doses of SP [13]. Another cross-sectional study involving 18,603 women aged between 15 and 49 years collected from the Malaria Indicator Surveys (MIS) conducted in Burkina Faso, Ghana, Mali, Malawi, Kenya, Nigeria, Sierra Leone, and Uganda showed an overall prevalence of 29.5% for taking three doses of IPTp-SP, with the prevalence being highest for Ghana (60%), followed by Kenya (37%) and Sierra Leone (31%) [14]. The Intermittent Preventive Treatment in pregnancy with SP is a key intervention recommended to reduce maternal malaria episodes, maternal and fetal anaemia, placental parasitaemia, low birth weight, and neonatal mortality among pregnant women living in sub-Saharan Africa [15]. IPT is provided as part of a comprehensive ANC package with other medicines like hematinics and antihelmintics. This provides maximum protection against maternal anaemia and morbidity, as well as low birth weight. It also reduces the risk of spontaneous abortion, stillbirth, and preterm deliveries [3]. The WHO recommendation where, after the first trimester, every pregnant woman should receive the recommended doses of SP at every ANC visit, beginning the first dose at 13-16th weeks of pregnancy, and the next five doses at the 20th, 26th, 30th, 34th, and 38th weeks of gestation [16], under the supervision of a health worker by Directly Observed Therapy (DOT) [15,17].
With evidence of rise in the number of ANC visits and the adoption of the current IPTp-SP and DOT policy, it is expected that IPTp-SP uptake will be high, thereby reducing the prevalence of malaria in pregnancy and its associated adverse effects [18]. However, in Ghana, pregnant women still present with malaria and maternal anaemia [19,20]. This study therefore evaluated the factors that influence uptake of IPTp-SP among pregnant women at the Kwame Nkrumah University of Science and Technology Hospital in Kumasi, Ghana. Kumasi is Ghana's second largest city in Ghana and lies between latitude 6.35 ∘ N and 6.40 ∘ N and longitude 1.3 ∘ W and 1.35 ∘ W. It is 150sq km in size and located in the rainforest zone of West Africa with a population of about 2 million inhabitants [21].

Materials and Methods
The Ashanti region has an intense perennial malaria transmission, with the predominant parasite being P. falciparum. Kumasi recorded the highest number of malaria cases (297,242 cases) in 2011 while the lowest recorded was 217,861 cases (in 2015) [22]. The prevalence of malaria in pregnancy was 36.3% in 2009 [23]. At the KNUST Hospital, the prevalence was 12.6% in 2013 [24].

Study Population.
A total of 280 pregnant women visiting the antenatal unit of the Hospital were recruited for the study. The sample size was calculated using the Raosoft sample size calculator [25]. The minimum sample size required for this study was 196 participants at 95% confidence level, 7% margin of error, and a response distribution of 50%.

Ethical Considerations.
Ethical approval was obtained from the Committee on Human Research Publication and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology (CHPRE/RC/131/16), and the Institutional Review Board of the Kwame Nkrumah University of Science and Technology Hospital. All participants gave their written informed consent after the aim of the study had been explained to them.

Inclusion and Exclusion Criteria.
Pregnant women of all ages who consented after the aim and objectives had been explained to them were recruited for the study. Critically illpregnant women were excluded.

Questionnaire Administration.
A well-structured questionnaire was validated and administered to the study participants within the framework of the study variables consisting of demographic information (age, residence, and parity), socioeconomic status (occupation, education, and religion), the awareness of the IPT program, ANC visit, and IPTp-SP doses. Data were collected using an investigatoradministered questionnaire in a language that they could easily comprehend.

Data Analysis.
All categorical variables were presented as frequencies (percentages) and continuous variables as Means ± SD. Multivariate logistic regression analysis was used to evaluate the factors that influence ANC visit and completion of the recommended IPTp-SP dose. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 25.0. Table 1 shows the sociodemographic characteristics and IPTp-SP uptake of the study population
The association between sociodemographic characteristics, medical history, and ANC visits is shown in Table 2. Cohabitation [aOR= 9.2, 95% CI (0.83-101.94)] was associated with increased odds of ANC visits and having three children [aOR = 0.23, 95% CI (0.04-1. 19)] was associated with decreased odds of ANC visits, with borderline significance ( Table 2). Table 3 shows association between sociodemographic characteristics, medical history, and ANC IPT dose completion. The age of the participants, their religion and marital status, and directly observed therapy did not significantly influence the IPT dose completion. Pregnant women with tertiary education [aOR=3. 15

Discussion
ANC attendance and, subsequently, the uptake of intermittent preventive treatment to reduce the prevalence of malaria in pregnancy are expected to improve with the implementation of the current IPTp-SP and DOT policy. Nevertheless, current studies in Ghana show that the prevalence of malaria in pregnancy is still high [26,27]. At the KNUST Hospital, the prevalence was 12.6% in 2013 [24]. This study therefore evaluated the factors that influence uptake of IPTp-SP among pregnant women at the University Hospital in Kumasi, Ghana.
Most of the respondents were within the child bearing age of 26-30 years, married, and primiparous (Table 1), consistent with an earlier study in Ghana by Doku and coworkers [28].
It was observed from this study that ANC attendance ranged from 2-12 visits with most of the participants (74.6%) making four or more visits ( Table 2). This study shows an increased ANC attendance, similar to cross-sectional studies by Gross et al. [29] in Tanzania and Bouyou-Akotet et al., in Gabon [30]. This high attendance rate offers the potential for implementing the nationally recommended approaches to curbing malaria among Ghanaian pregnant women. Additionally, WHO also recommends that, after the first trimester, every pregnant woman should receive the recommended doses of SP at every ANC visit, beginning the first dose at 13-16th weeks of pregnancy and the next five doses at the 20th, 26th, 30th, 34th, and 38th weeks of gestation [16].
Findings from this study also show that cohabiting respondents [aOR= 9.2, 95% CI (0.83-101.94)] were more likely to attend the ANC compared to single women ( Table 2). This corroborates a study in South-Eastern Tanzania which reported that marital status is an independent factor that influences the frequency of ANC visits [29]. Furthermore, the same study identified that not being supported by a spouse was a factor associated with a late antenatal care enrollment, buttressing the effect of companionship on ANC attendance [29]. Moreover, a cross-sectional study conducted in Ghana noted that husbands played an economic role in the frequency of a pregnant women's ANC visits with some men taking up the responsibility of maintaining the wellbeing of their pregnant wives by ensuring that they attend ANC clinics, whiles adolescent pregnant girls are less likely to attend an ANC and seek timely healthcare [31,32] due to stigmatization and financial constraints.
The World Malaria Report has over the years indicated an improvement in IPT coverage among pregnant women in sub-Saharan Africa, with a recent coverage of 19% in 2016 [18]. According the Demographic Health Survey, Ghana made significant strides in improving IPT uptake from 26.8% in 2008 to 38.5% in 2014 [33,34]. This current study observed a higher coverage of 31.8% (Table 3). The coverage in this study is lower compared to a recent cross-sectional hospitalbased study by Owusu-Boateng, and Anto among Ghanaians [35]. They reported a higher coverage of IPT3 (87.5%), IPT4 (55.7%), and IPT5 (14.5%); a discrepancy that may be attributed to the fact that their study was conducted in the national capital, Accra, where most people are educated and policy implementation is effective compared to our study area. Notwithstanding the higher coverage in this, there is the need for improved IPT administration, as the coverage is far below the targeted coverage of 100% [36]. Anchang-Kimbi et al., in 2014, suggested that late first ANC clinic enrollment and fewer clinic visits may prevent the uptake of SP; however education on early and regular ANC clinic visits may increase IPTp coverage [37]. Other studies have however reported a negative influence of education on ANC visit and IPTp -SP uptake [38,39]. This study, on the contrary, observed that pregnant women with tertiary level of education [aOR=3.15, 95% CI (0.94 -10.97), and p=0.042] were more likely to complete the recommended IPTp-SP dose in comparison to the uneducated (Table 3), consistent with other studies [40][41][42][43][44][45]. This association may be attributed to the ability of the educated to understand health information as well as its significance and hence adherence to the recommended dose [46][47][48].
However, women who worked in the formal sector [aOR=0.28, 95% CI (0.09 -0.79), and p=0.016] were less likely to complete recommended SP dose compared to the informally employed (Table 3). This may be attributed to the fact that women employed in the formal sector work under strict conditions and are not at liberty to leave their jobs to attend the antenatal clinics [29].
Our study also shows that primiparous women were less likely to complete the recommended dose of SP [aOR=0.33, 95% CI (0.14 -0.77), and p=0.010] compared with women with no child (Table 3). This finding is in consonance with reports by Kuile et al, [49] and Olorunda, [50] who indicated that have only one child are less likely to use malaria preventive measures due to their younger age. Moreover, women with more than four children [aOR=0.14, 95% CI (0.03 -0.63), p=0.011] were also less likely to complete the recommended IPTp-SP dose (Table 3). Furthermore, higher number of ANC visits [aOR=24.6, 95% CI (5.87-103.07), p<0.0001] positively influenced the uptake of the recommended IPT dose (Table 3). This is in consonance with a cross-sectional study by Bouyou-Akotet et al., in 2013 among Gabonese [30], and Nkoka et al. among Malawian women [51]. Nonetheless, the finding of this study contradicts a cross-sectional study by Toure et al. in Côte d'Ivoire [52]; however, SP stock shortage, absence of cups and clean drinking water for taking SP by DOT, unclear guidelines or confusion among health workers regarding the guidelines, and other related health facility factors were the factors attributed to the hindrance of the IPTp delivery.
This study is limited by the fact that some of the responses provided by the participants may not be accurate due to fear of incrimination. However, participants were assured of privacy and confidentiality of the information they provided. Another limitation of this study is that it was done in an urban setting and might not be generalizable to other areas especially rural areas. Furthermore, factors such as availability of drugs at the health facility and health workers' performance that may have influence IPT-SP uptake were not assessed. Moreover, the study area was a large tertiary hospital and women might be from different areas that might differ in malaria endemicity.

Conclusion
ANC attendance is critical in IPTp uptake. The results emphasize the need for the Health Policy Makers in Kumasi to encourage pregnant women, especially women working in the formal sector and women having more than four children to patronize ANC attendance to ensure high coverage of the recommended IPTp dose.

Data Availability
All relevant data are within the article.

Conflicts of Interest
The authors declare that they have no conflicts of interest.

Authors' Contributions
Otchere Addai-Mensah, the PI, designed the study, supervised the research and laboratory analysis, drafted the manuscript, and revised it. Max Efui Annani-Akollor, Linda Ahenkorah Fondjo, Kwadwo Sarbeng, and Shanice Nglokie Arthur were involved in the design of the study, collection of data, laboratory analysis, and drafting and revision of the manuscript. Enoch Odame Anto and Eddie-Williams Owiredu were involved in the design of the study, collection of data, and statistical analysis. All authors read and approved the final manuscript.