Prevalence, associated factors, and pharmacotherapy of hypertensive disorders among parturients in Bono Region of Ghana: An analytical cross-sectional study

1 Prevalence, associated factors, and 2 pharmacotherapy of hypertensive 3 disorders among parturients in Bono 4 Region of Ghana: An analytical cross- 5 sectional study 6 7 8 Authors: Francis Fordjour 1, #a, 2, #b ¶*, Edward Tieru Dassah3 ¶, Jonathan Boakye -Yiadom4&, 9 Kwadwo Addai-Darko5&, Bernard Okyere5&, Kwame Ohene Buabeng2, #b, 6, #a ¶ 10 11 Authors’ affiliations: 12 13 1 Department of Pharmaceutical Sciences, Faculty of Applied Science, Sunyani Technical 14 University, Sunyani, Bono Region, Ghana. 15 2 Department of Pharmacy Practice, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame 16 Nkrumah University of Science and Technology (KNUST), Kumasi, Ashanti Region, Ghana. 17 3 Department of Population, Family and Reproductive Health, School of Public Health, Kwame 18 Nkrumah University of Science and Technology (KNUST), Kumasi, Ashanti Region, Ghana. 19 4 Department of Epidemiology and Biostatistics, School of Public Health, Kwame Nkrumah 20 University of Science and Technology (KNUST), Kumasi, Ashanti Region, Ghana. 21 5 Department of Obstetrics and Gynecology, Sunyani Teaching Hospital, Sunyani, Bono Region, 22 Ghana. 23 6 School of Pharmacy, University of Health and Allied Sciences, Ho, Volta Region, Ghana. 24 25 * Corresponding author 26 E-mail: [email protected] (FF) 27 ORCID ID: 0000-0002-7651-162X 28 ¶ These authors contributed equally to this work 29 &These authors also contributed equally . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 30 Abstract 31 Background: The burden of hypertensive disorders among parturients in remote locations of 32 Ghana remains understudied, considering existing data. We investigated the prevalence, associated 33 factors, and treatment guideline’s adherence for maternal hypertensive disorders among parturients 34 in a peripheral region. 35 Method: In an analytical cross-sectional study, data of all parturients with hypertensive disorders 36 were extracted from labor registers of nine public hospitals in the Bono Region of Ghana from 37 January to December 2021. Additionally, guidelines for administering magnesium sulfate and 38 antihypertensives to these patients were examined. Chi-square and multivariable binomial 39 regression analyses were used to explore associations between independent and dependent 40 variables. P ≤ 0.05 was considered statistically significant. 41 Results: Hypertensive pregnancies were 711 out of 16,206 deliveries, with a prevalence of 4.4%. 42 Non-severe pre-eclampsia (30.5%) and gestational hypertension (28.0%) were the most frequent 43 disorders. Eclampsia (6.2%) and superimposed pre-eclampsia (1.7%) were less frequent. Maternal 44 age, 15-25 years (cOR = 2.43; 95% CI = 1.57-3.75; p < 0.001), unemployment (cOR = 2.14; 95% 45 CI = 1.29-3.53; p = 0.001), primigravida (cOR = 2.88; 95% CI = 1.80-4.62; p < 0.001), and 46 primiparity (cOR = 2.39; 95% CI = 1.44-3.96; p < 0.001) were significantly associated with pre- 47 eclampsia/eclampsia. After adjustment for confounders, primiparity remained a borderline 48 significant predictor (aOR = 1.83; 95% CI= 0.97-3.46; p = 0.05). Oral nifedipine (30mg) and 49 intravenous hydralazine were the primary medications for pregnant hypertensives. Magnesium 50 sulfate was universally administered by the Pritchard procedure, but product concentrations 51 supplied by pharmacists for intramuscular application varied minimally. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 52 Conclusion: The prevalence of hypertensive disorders among parturients was 4.4%. Young 53 parturient age, unemployment, primigravida, and primiparity were the predictors. Magnesium 54 sulfate protocols for managing pre-eclampsia/eclampsia cases followed a standard regimen. 55 Standardizing the concentration of magnesium sulfate solutions for pre-eclampsia/eclampsia could 56 optimize intramuscular dosing under the Pritchard regimen, improving treatment consistency. 57 Introduction 58 Hypertensive disorders in pregnancy (HDPs) continue to hinder the course of many pregnancies 59 resulting in abrupt interventions, complications and mortalities with a potential of undermining 60 target 3.1 of the Sustainable Development Goals (SDG) (1). The spectrum of HDPs, which varies 61 from chronic, gestational, pre-eclampsia/eclampsia and superimposed pre-eclampsia, impact 62 women health worldwide and have had significant repercussions for low-income nations (2,3) 63 These disorders have become topical recently due to the rise in cases that have been documented 64 and the unfavorable consequences they have in certain nations (4,5). The incidence of HDPs has 65 increased by 10.92% globally over the last three decades, having risen from 16.30 million in 1990 66 to 18.08 million in 2019 (4). 67 Given that almost a third of affected women nearly die, particularly in nations with limited 68 resources, this rising trend is extremely concerning and unnecessarily causes panic among 69 parturients and medical personnel (6). Hypertensive disorders of pregnancy together with 70 hemorrhage, sepsis, and unsafe abortions are major contributors to the maternal death ratio in low- 71 income countries (7,8), surpassing the SDGs' estimate by more than six-fold (1). 72 According to World Health Organization (WHO) data (9), Ghana still has a high maternal 73 mortality ratio (263/100,000), and the country's rising HDP burden adds to these deaths (10). 74 Studies available on the subject almost a decade ago suggest that the incidence of HDPs in Ghana's . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 75 Upper West and Greater Accra regions is less than 10% (11). However, the prevalence was high 76 when explored in 2019 and 2017 at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, 77 Ghana, and the Korle-Bu Teaching Hospital (KBTH) in Accra respectively (12,13). In Ghana, it 78 is reported that over a third of women with HDPs experience ‘near-death’ episodes; the ratio of 79 these incidents to death is approximately 12:1 (14). Despite the negative impact, it appears that the 80 majority of research looking for HDPs in Ghana concentrate on tertiary hospitals, with little 81 information published from lower-tier facilities, particularly those located in the rural and smaller 82 administrative regions. There is a need to close this information gap because it is argued that the 83 unavailability of published statistics on HDPs in smaller regions significantly affects regional and 84 global estimations which may mislead policies (15). 85 Many maternal deaths, including those caused by HDPs in sub-Saharan Africa, are listed by the 86 WHO as avoidable, implicating care plans offered to maternal hypertensives in the sub-region (8). 87 The essential ideas that underpin the management of HDPs worldwide include early antenatal 88 screening for case identification, antihypertensive therapy, the administration of anticonvulsants, 89 and timely baby delivery. However, the way these concepts are applied may vary based on the 90 resources, patient characteristics, and skill set that are available in a given geographical area. 91 Inconsistencies were found in post-implementation studies involving the administration of 92 magnesium sulfate (MgSO 4) to women who were eclamptic. Some nations lacked the necessary 93 skills to safely administer the product, while others had difficulties with product accessibility. 94 Furthermore, some institutions lacked treatment-guided protocols for MgSO 4 application, which 95 hindered the safe use of the anticonvulsant in nations that have high rates of HDPs (16,17). Ghana's 96 standard treatment guideline (STG) incorporates all of the fundamental HDP management 97 principles; nevertheless, there aren't many post-implementation studies assessing these in . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 98 healthcare institutions. In this study, we reviewed practice guidelines on the use of MgSO 4 and 99 antihypertensives for HDPs as well as the prevalence and factors associated with these disorders 100 among parturients in the Bono Region. 101 Materials and method 102 Study design and setting 103 An analytical cross-sectional study design was employed in which obstetric records, particularly 104 labor registers, and institutional treatment protocols for HDPs were monitored retrospectively for 105 data in nine public hospitals of the region. The Sunyani Municipal, Sunyani SDA, Bono Regional, 106 Berekum Holy Family, Dormaa Presbyterian, Drobo St. Mary’s Catholic, Sampa Government, 107 Tain District, and the Wenchi Methodist Hospitals were the purposefully chosen research facilities. 108 These hospitals were selected because they provided important obstetric services in eight of the 109 region's twelve administrative districts and were the most established and resourced facilities. 110 Health facilities in four districts were at the time of data collection not included due to their status 111 as health centers which could not fully manage HDPs. The nine hospitals had a maternal bed 112 capacity of 384 and conducted about 1800 deliveries annually. 113 The Bono Region is located on Ghana's middle belt zone, sharing an international boundary to the 114 west with the Republic of Cote d'Ivoire and to the north and south with Ghana's Savannah and 115 Ashanti regions, respectively. With a population of roughly 1,208,649, the region occupies an area 116 of 11,113 km2 (18). Its residents are primarily famers and traders. 117 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 118 Study population and Sample 119 All pregnant women who were registered and delivered at the public hospitals in Bono Region of 120 Ghana between 3 rd January 2021, and 31 st December 2021, were considered. Overall, 16,206 121 deliveries were conducted within the period of which 711 women presented with various HDPs. 122 All 711 parturients diagnosed with HDPs during the study period were included in the study. 123 Women with incomplete records during the review were excluded. 124 125 Data collection 126 Data of parturients was extracted from the labor registers of the hospitals using a designed 127 template. Women’s age, level of education, occupation, parity, gestational ages at labor, and the 128 kind of HDP identified were among the information collected. Additionally, each hospital's 129 institutional guideline for treating the spectrum of HDPs was reviewed, and with informed consent, 130 the heads of the various labor wards filled questionnaire on the use of anti-HDP drugs. The 131 questionnaire was about antihypertensive and anticonvulsant medication availability and their 132 usage for treating HDPs, particularly pre-eclampsia/eclampsia. It required the names of all 133 medicines, their dosage forms, pharmaceutical strengths, and how they were administered. 134 Importantly, requests were made for institutional MgSO4 protocols and administration procedures 135 including loading and maintenance doses, and their concentrations when given intravenously (IV) 136 or intramuscularly (IM). Further, unit leaders answered questions on serum concentration 137 monitoring of MgSO 4, adverse effects and toxicity monitoring in both open and closed-ended 138 questions. 139 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 140 Ethical Approval 141 Permission to obtain data from the institutions in the Bono Region was granted by the Bono 142 Regional Health Directorate, and ethical approval was sought and obtained from the Committee 143 on Human Research Publication and Ethics of KNUST (Ref: CHRPE/AP/119/20). Authors had no 144 access to the identities of individual participants whose data were collected, and informed consent 145 was obtained from labor ward in-charges/doctors where questionnaires required completion. 146 Data analysis 147 The data was analyzed using Stata 17.0 (Stata Corporation, Texas, USA). Categorical variables 148 were compared using Chi-square (𝜒2) or Fisher’s exact tests, as appropriate. Binomial regression 149 with a log-link function was used to estimate crude and adjusted odds with 95% confidence 150 intervals (CIs) for factors associated with hypertensive disorders in pregnancy (HDPs). The dataset 151 that supports the findings of this study has been attached under the supporting information section 152 as S1 file_Dataset.xlsx. Missing data was excluded, and results with p-values ≤ 0.05 were 153 considered statistically significant. 154 155 Diagnoses of HDPs according to the standard treatment guideline of 156 Ghana 157 According to Ghana's STG, a pregnant woman has a hypertensive disorder when her blood 158 pressure (BP) is ≥ 140/90 mmHg on two or more occasions, spaced at least five minutes apart, 159 using an appropriate BP monitoring device (19). The diagnoses of gestational hypertension, 160 chronic hypertension, pre-eclampsia with or without severe features, superposed pre-eclampsia 161 and eclampsia may be made based on the timing of the onset of the hypertensive BP relative to the . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 162 gestational age, time to conception, the patient's signs and symptoms, and any biochemical 163 assessment suggesting an organ dysfunction. Gestational hypertension is new onset, occurring 164 after mid-gestation without proteinuria or classical signs and symptoms; chronic hypertension is 165 similarly symptomless, carried into pregnancy or identified in the first 20 weeks of gestation, 166 unassociated with proteinuria, and persists after labor. A non-severe and severe forms exist in pre- 167 eclampsia. Usually, it begins during mid-gestation with a fresh onset of hypertension (SBP ≥ 168 140/DBP ≥ 90 mmHg) and mild proteinuria. It becomes severe if there are neurological signs and 169 symptoms, massive proteinuria, elevated BP (SBP > 160/DBP ≥ 110 mmHg), or biomarkers 170 related to target organ injury. Women with chronic hypertension are diagnosed with superimposed 171 pre-eclampsia if their features align with pre-eclampsia while eclampsia is diagnosed if a pre- 172 eclamptic woman experiences seizures without other identifiable reasons (19). It is highlighted 173 that screening for soluble fm-like tyrosine kinase-1 (sFlt-1) and placental growth factors (PlGF) is 174 also accessible for diagnosing HDPs in advance settings but non-existent in the region at the time 175 of data collection. 176 177 Pharmacotherapy of HDPs per the guidelines of Ghana 178 Under Ghanaian treatment policy, methyldopa and sustained release/retarded nifedipine are 179 prescribed for mild hypertensive cases in pregnancy (BP 140/90-159/109 mmHg). The 180 recommended treatments for severe maternal hypertension are IV hydralazine, and labetalol. To 181 abort seizures or prevent same, MgSO4 by the Pritchard approach is recommended. This protocol 182 administers the drug in two phases: an IV loading and IM maintenance doses. During loading, 14g 183 of the anticonvulsant is administered as 4g IV in a 20% MgSO 4 solution at first, with 2 doses of 184 5g IM in a 50% solution into each buttock (10g). Subsequently, series of 5g IM doses of a 50% 185 solution are injected into alternate buttocks every four hours to initiate the maintenance phase. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 186 This begins four hours after the loading dose has been initiated and continuously administered for 187 24 hours for preventive therapies or 24 hours after the last fit (19). 188 189 Results 190 Level of care of the Health Facilities involved in the study 191 Primary care level health services were provided by eight of the nine hospitals in rural and semi- 192 urban communities of the region. The ninth establishment was a regional hospital that provided 193 specialist services and doubled as the referral center for the Bono Region of Ghana. 194 195 Parturients’ sociodemographic and obstetric data 196 Table 1 presents the sociodemographic data of parturients. The age range was 15-46 years and the 197 mean age was 30.9789 (±6.80541). Those aged 26-34 years made up the largest proportion 198 (43.9%). The majority were those who attained basic education (61.7%), working in informal 199 occupations (68.0%), multigravida (51.9%), and multiparous women (53.0%). 200 201 202 203 204 205 206 207 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 208 209 210 211 212 Table 1. Sociodemographic data of women involved in the study Variable Number of women (n=711) n(%) Age group (years) 15-25 151 (21.2) 26-34 312 (43.9) 35-46 248 (34.9) Educational level Basic 439 (61.7) Secondary 124 (17.4) Post-secondary/tertiary 148 (20.8) Occupation Unemployed 89(12.5) Informal employment 483(68.0) Formal employment 139(19.5) Gravida Primigravida 135 (19.0) Multigravida 369 (51.9) Grand multigravida 207 (29.1) Parity Primiparous 248 (34.9) Multiparous 377 (53.0) Grand multiparous 86 (12.1) Gestational age at delivery First trimester 8 (1.1) Second trimester 18 (2.5) Third trimester 685 (96.3) 213 214 215 Types of hypertensive disorders diagnosed among parturients 216 A sum of 16,206 deliveries were conducted in the nine hospitals: 711 were diagnosed with HDPs. 217 A prevalence of 4.4% was observed. From Fig 1, the commonest HDP among the parturients was 218 pre-eclampsia. This occurred without severe features in 30.5% of the subjects but in 21.0%, it was . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 219 associated with severe features. Gestational hypertension was found among 28.0%, whereas 6.2% 220 developed eclampsia. 221 222 223 224 Fig 1. Patients’ diagnoses 225 226 Maternal demographic data compared with diagnoses 227 Table 2 summarizes the distribution of HDPs across parturients’ demographic variables. Chronic 228 hypertension was conspicuous among women aged 35-46 years (53.3%), basic education attainers 229 (60.0%) and multiparous women (62.2%). Gestational hypertension was prevalent among women 230 aged 26-34 years (45.2%), the least educated (65.8%) and multiparous as well (58.8%). Pre- 231 eclamptic disorders (non-severe, severe, and superimposed) were seen mostly in middle-aged 232 women (46.8%) between 26-34 years, those with low literacy (59.0%), multigravida (54.2%) and 233 multiparous (52.1%). The majority of eclamptics (68.2%) were in the 15-25 age group, the least 234 educated (70.5%), and primiparous (77.3%) who had delivered for the first time. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 235 Table 2. A comparison of hypertensive disorders with maternal sociodemographic characteristics Variable Chronic hypertension (n=90) n(%) Gestational hypertension (n=199) n(%) Pre-eclampsia (n=378) n(%) Eclampsia (n=44) n(%) Age 15-25 5 (5.6) 37 (18.6) 79 (20.9) 30 (68.2) 26-34 37 (41.1) 90 (45.2) 177 (46.8) 8 (18.2) 35-46 48 (53.3) 72 (36.2) 122 (32.3) 6 (13.6) Educational level Basic 54 (60.0) 131 (65.8) 223 (59.0) 31 (70.5) Secondary 19 (21.1) 25 (12.6) 70 (18.5) 10 (22.7) Post-secondary/tertiary 17 (18.9) 43 (21.6) 85 (22.5) 3 (6.8) Occupation Unemployed 2 (2.2) 21 (10.6) 47 (12.4) 19 (43.2) Employed 88 (97.8) 178 (89.4) 331 (87.6) 25 (56.8) Gravida Primigravida 5 (5.6) 30 (15.1) 74 (19.6) 26 (59.1) Multigravida 45 (50.0) 105 (52.8) 205 (54.2) 14 (31.8) Grand multigravida 40 (44.4) 64 (32.2) 99 (26.2) 4 (9.1) Parity Primiparous 16 (17.8) 57 (28.6) 141 (37.3) 34 (77.3) Multiparous 56 (62.2) 117 (58.8) 197 (52.1) 7 (15.9) Grand multiparous 18 (20.0) 25 (12.6) 40 (10.6) 3 (6.8) Gestational age First trimester 7 (7.8) 1 (0.5) 0 (0.0) 0 (0.0) Second trimester 7 (7.8) 2 (1.0) 7 (1.9) 2 (4.5) Third trimester 76 (84.4) 196 (98.5) 371 (98.1) 42 (95.5) . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 237 Factors associated with hypertensive disorders during pregnancy 238 The associations between parturients’ characteristics and hypertensive disorders are presented in 239 Table 3. Age was significantly associated with hypertensive disorders during pregnancy (p<0.001). 240 Younger women aged 15-25 years (25.8%), were observed more frequently with pre- 241 eclampsia/eclampsia, whereas older women aged 35-46 years (41.5%), were more common in the 242 chronic/gestational hypertension group. Maternal employment status also showed a significant 243 association (p=0.002). A higher proportion of the unemployed (15.6%) were in the pre- 244 eclampsia/eclampsia category, while those in employment (92.0%) dominated in the 245 chronic/gestational hypertension group. Gravidity and parity were strongly associated with 246 hypertensive disorders (p<0.001). Primigravida (23.7%) or primiparous women (41.5%), were 247 more linked to pre-eclampsia/eclampsia. In contrast, grand multigravida women (36.0%) and 248 multiparous women (59.9%) were more represented in the chronic/gestational hypertension group. 249 However, the educational status of a parturient did not significantly impact the type of a 250 hypertensive disorder (p = 0.411). 251 252 253 254 255 256 257 258 259 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 260 261 Table 3. Parturients’ factors and their association with hypertensive disorders (n=711) Variable Chronic/gestational hypertension Pre-eclampsia/ eclampsia p-value Age <0.001 15-25 42 (14.5) 109 (25.8) 26-34 127 (43.9) 185 (43.8) 35-46 120 (41.5) 128 (30.3) Educational level 0.411 Basic 185 (64.0) 254 (60.2) Secondary 44 (15.2) 80 (19.0) Post-secondary/tertiary 60 (20.8) 88 (20.9) Occupation 0.002 Unemployed 23 (8.0) 66 (15.6) Employed 266 (92.0) 356 (84.4) Gravida <0.001 Primigravida 35 (12.1) 100 (23.7) Multigravida 150 (51.9) 219 (51.9) Grand multigravida 104 (36.0) 103 (24.4) Parity <0.001 Primiparous 73 (25.3) 175 (41.5) Multiparous 173 (59.9) 204 (48.3) Grand multiparous 43 (14.9) 43 (10.2) Trimester of pregnancy 0.001* First trimester 8 (2.8) 0 (0.0) Second trimester 9 (3.1) 9 (2.1) Third trimester 272 (94.1) 413 (97.9) 262 Note: * (Fisher’s exact) 263 264 Parturients’ odds of developing a hypertensive disorder 265 Table 4 examines the odds of a parturient developing pre-eclampsia/eclampsia based on 266 sociodemographic and obstetric factors. Early maternal age (15-25 years) was 2.43 times more 267 related to pre-eclampsia/eclampsia (cOR = 2.43; 95% CI: 1.57-3.75 p = < 0.001) compared to 268 older parturient age (35-46 years). Unemployed parturients were twice likely to have pre- 269 eclampsia/eclampsia (cOR = 2.14; 95% CI=1.29-3.53; p = 0.001). Primigravidity elevated the odds . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 270 to almost three times that of grand multi-gravida women (cOR =2.88; 95% CI: 1.80-4.62, p < 271 0.001). Primiparity also doubled the odds (cOR = 2.39, 95% CI: 1.44 -3.96; p = <0.001) and after 272 adjusting for potential confounders, primiparity remained a significant predictor though with a 273 marginal significance level (aOR = 1.83; 95% CI: 0.97–3.46, p-value = 0.05). The educational 274 level of a parturient did not significantly impact the odds of developing pre-eclampsia/eclampsia. 275 Table 4. Regression analysis of the association between maternal sociodemographic data with pre-eclampsia/eclampsia Variable Pre-eclampsia /Eclampsia cOR 95% CI p-value aOR 95% CI p-value Age 0<0.001 0.37 15-25 109 (72.2) 2.43 1.57-3.75 1.51 0.84-2.72 26-34 185 (59.3) 1.36 0.97-1.91 1.14 0.78-1.67 35-46 128 (51.6) 1 1 Educational level 0.40 Basic 254 (57.86) 1 Secondary 80 (64.52) 1.32 0.88-2.00 Post- secondary/tertiary 88 (59.46) 1.07 0.73-1.56 Occupation 0.001 Unemployed 66 (74.16) 2.14 1.29-3.53 Employed 356 (57.23) 1 Gravida 0<0.001 Primigravida 100 (74.07) 2.88 1.80-4.62 Multigravida 219 (59.35) 1.47 1.04-2.07 Grand multigravida 103 (49.76) 1 Parity 0<0.001 0.05 Primiparous 175 (70.56) 2.39 1.44-3.96 1.83 0.97-3.46 Multiparous 204 (54.11) 1.17 0.73-1.88 1.09 0.66-1.80 Grand multiparous 43 (50.00) 1 1 Trimester of pregnancy 0.38 Second trimester 9 (50.00) 1 Third trimester 413 (60.29) 0.65 0.25-1.68 aOR, adjusted odds ratio; cOR, crude odds ratio; CI, confidence interval; p, probability . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 16 277 Availability and use of antihypertensive medications for the 278 pregnant women at the hospitals 279 Methyldopa and the sustained-release nifedipine were the common oral antihypertensive 280 medicines available in all facilities for HDPs. The sustained release oral nifedipine (30mg) was 281 used by seven hospitals as first choice agent for HDPs, particularly pre-eclampsia. Intravenous 282 hydralazine (20mg/ml) was available and used in all the hospitals for severe cases of pre- 283 eclampsia. Four out of nine hospitals had IV labetalol (100mg/20ml) as an alternative (Table 5). 284 285 Table 5. Antihypertensive medicines available in the hospitals for managing hypertension 286 in pregnancy Medicines Number of hospitals that use the agent (n=9) Used as first choice agent (n=9) Orals Methyldopa 250mg 9 2 Nifedipine retard 20mg 5 0 Extended release nifedipine 30mg 9 7 Oral Hydralazine 25mg 2 0 Oral Labetalol 50mg/100mg 0 0 Parenteral agents IV hydralazine (20mg/ml) 9 9 IV labetalol(100mg/20ml) 4 0 287 IV, intravenous 288 289 Usage of magnesium sulfate as anticonvulsant for pre- 290 eclampsia/eclampsia 291 All the nine hospitals had stocks of MgSO4 injectables for managing pre-eclampsia/eclampsia. The 292 50% solution (10ml ampoule) was available in 8/9 facilities and protocols in the form of posters 293 for administering same were conspicuous in all labor wards. The Pritchard regimen was the norm 294 across facilities. Loading doses were unanimously 14g; injected as 4g IV followed by 10g IM. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 17 295 Maintenance doses were 5g IM, given four hourly apart. The 50% MgSO 4 solution was used for 296 IM maintenance doses while IV doses were administered with a 20% solution. One hospital had 297 in addition to the 50% protocol, another protocol that allowed a 20% solution to be used to inject 298 5g IM doses. Per all protocols examined, MgSO4 prophylactic treatment was completed 24 hours 299 after initiating the loading and administering a series of 6 IM maintenance doses. When the loading 300 and maintenance doses are put together, each patient receives 44g of the salt within 24 hours. 301 Testing renal function of patients at the point of initiating MgSO4 therapy was not always done in 302 any of the hospitals. All facilities lacked the capacity to monitor serum concentrations of 303 magnesium ions in women on treatment. Therapy monitoring was solely based on patient 304 sign/symptoms such as knee jerk responses, respiratory rate and urine output. Seven out of the nine 305 hospitals had usable calcium gluconate injectables to manage MgSO4 toxicities (Table 6). 306 307 308 309 310 311 312 313 314 315 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 18 316 317 Table 6. Usage of MgSO4 to manage pre-eclampsia/eclampsia by hospitals in Bono Region MgSO4 Usage Facility (n=9) Presence of MgSO4 injectable at hospital Yes 9 Type of stocks present at the time 50% MgSO4 (10ml ampoule) 8 20% MgSO4 (10ml ampoule) 1 Treatment protocol pasted at labor ward Yes 9 Type of treatment regimen Loading dose + maintenance doses 9 Composition of loading dose 4g IV + 10g IM 9 Concentration of MgSO4 by IV route 20% 9 50% 0 Maintenance doses 5g IM 4 hourly 9 Concentration of MgSO4 by IM route 50% 8 20% 1 Injection site for IM doses Buttocks 9 Completion of treatment regimen After 6 IM maintenance doses injected 4 hourly 9 Maximum dose of MgSO4 administered to a patient 44g 9 Renal function test results seen before starting MgSO4 Always 0 Sometimes 9 Patient monitoring Solely based on patient signs and symptoms 9 Serum concentrations of Mg2+ 0 Availability of calcium gluconate to manage toxicity Yes 7 No 0 Expired 2 318 IM, Intramuscular; IV, Intravenous; MgSO4, Magnesium sulfate 319 320 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 19 321 Discussion 322 This study highlights the prevalence of hypertensive disorders among parturients in the Bono 323 Region of Ghana and examines how these disorders were managed at service delivery points using 324 antihypertensive and anticonvulsant medicines. The need for the study arose from the lack of 325 published data on HDPs in the region, which made it challenging to quantify the burden and 326 compare same with other smaller regions of Ghana. Additionally, several years after the adoption 327 of WHO-recommended treatment guidelines by Ghana, there have been limited post- 328 implementation studies evaluating the administration of MgSO 4 for pre-eclamptic/eclamptic 329 patients. The study addresses these knowledge gaps. 330 Our results indicate that the prevalence of HDPs in the Bono Region was 4.4%, a rate less than 331 those reported in Zambia (6.7%), Ethiopia (6.82%), sub-Saharan Africa (8%), and Nigeria (25.8%) 332 (20–23). However, it was higher than Burkina Faso (1.4%) and Ghana's Upper West Region 333 (3.2%) (11,24). The observed regional variations could be due to differences in study 334 methodologies, environmental and socioeconomic factors. Unlike studies that collected data from 335 antenatal clinics (ANCs) attendees, our study focused on data from women in labor, potentially 336 influencing prevalence estimates. Hospital deliveries in most Ghanaian facilities usually rank 337 lower than ANC attendance which may contribute to differences in findings (25,26). This may be 338 due to factors such as transportation challenges, financial constraints, fear of cesarean section, and 339 some negative perceptions of hospital staff attitudes which could contribute to home deliveries in 340 rural settings, leading to an underestimation of HDP prevalence in hospitals (25,26). However, in 341 Burkina Faso and the Upper West Region of Ghana, where the occurrences were lower than our 342 data, it seems that the effects of attendance and social characteristics were more prominent (11,24). . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 20 343 Pre-eclampsia was the most prevalent HDP in this study, consistent with findings of Dassah et al. 344 (2019) in Kumasi, Ghana (13). Among affected women, 30.5% had non-severe pre-eclampsia 345 while one-fifth had pre-eclampsia with severe features. These rates exceed the prevalence (4.1%) 346 estimated in a systematic review of sub-Saharan Africa indicating that our findings may reflect 347 regional differences in healthcare access and resources (22). Previous researchers showed that 348 HDPs were predicted by maternal age (27,28). Our multivariable regression analysis revealed a 349 significant association between age and HDP. Younger parturients (15-25 years) were more prone, 350 particularly to pre-eclampsia/eclampsia. Decreasing maternal age increased the odds, with over 351 two-thirds of eclamptic cases occurring in this age group (see Table 2). This trend is supported by 352 previous studies in Ghana and South Africa (29,30). The pathophysiological basis for this 353 association remains unclear but may involve mothers' aberrant immune responses to paternally 354 inherited fetal antigens during first pregnancies as hypothesized in earlier literature which could 355 apply to younger women getting pregnant for the first time (31). Additionally, reduced ANC 356 attendance among teenage mothers due to social stigma may lead to poor pregnancy monitoring, 357 anemia, and inadequate preventive care, further increasing their risk (28). Contrarily, our 358 advanced-aged parturients (≥ 35 years) were more aligned with chronic hypertension which was 359 consistent with existing literature (20,32,33). This is conceivable, given that obesity, vascular 360 calcification, stiffness, and loss of distensibility correlate with old age and greatly impact 361 hypertension (34). 362 The results of this study relates to previous authors who reported that parity plays a role in pre- 363 eclampsia/eclampsia (28,35). While our crude odds ratio indicated a significant association 364 between primigravidity and HDPs (p < 0.001), the adjusted odds showed significance for 365 primiparity (p = 0.05). Known in literature, multigravidity has been associated with a more . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 21 366 regulated immune response and adaptation to repeated exposure to paternally inherited antigens as 367 opposed to primigravid/primiparous women, who are first time encounters, less adapted and 368 therefore prone to inflammatory response leading to pre-eclampsia (31). Whereas parity was a 369 significant predictor, educational level did not show an association. Unlike some prior studies, our 370 findings did not establish a significant relationship between HDPs and illiteracy after adjusting for 371 other variables (27,28). The lack of variability in educational attainment among study participants 372 may have limited the statistical power to detect such an association. 373 Maternal hypertensives were primarily treated with the 30mg extended release nifedipine, 250mg 374 methyldopa, and IV hydralazine (20 mg/ml). These agents were consistently available across all 375 the nine hospitals. Among the available oral agents, nifedipine was the most commonly prescribed 376 first-line treatment in seven out of nine hospitals, mirroring prescribing patterns observed at 377 Tamale Teaching Hospital in Ghana (36). Its preference over methyldopa may be attributed to its 378 faster onset of action (30-45 minutes vs. 1-1.5 hours for methyldopa) (37–39). Oral labetalol was 379 rarely stocked, so its use for treatment was limited, likely due to cost and availability. Nifedipine’s 380 use was in line with Ghana's treatment policy, but some evidence suggests that nifedipine may 381 increase the risk of disease progression to pre-eclampsia when used in non-severe maternal 382 hypertension, prompting WHO to advocate for alternative oral agent such as labetalol in non- 383 severe hypertensive cases (40). 384 Some recently revised guidelines and review publications appear to place IV hydralazine as second 385 line agent for severe pre-eclampsia due to its perceived unfavorable kinetics and side effects, but 386 its utilization as first choice agent was evident in this study (41). The widespread usage was also 387 observation in Nigerian (42). The high utilization of IV hydralazine, despite recent guidelines 388 favoring IV labetalol may be driven by staff familiarity, affordability, and availability (43). . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 22 389 All study sites adhered to national and international guidelines recommending MgSO₄ for 390 managing severe pre-eclampsia/eclampsia (19,44). All hospitals had access to the product, along 391 with its administration protocols. The Pritchard regimen was uniformly followed, likely due to its 392 convenience and independence from infusion pumps, which are often scarce in resource-limited 393 settings (19). Magnesium sulfate is administered to severe pre-eclamptic women not because they 394 have Mg2+ deficiency, but rather to raise Mg2+ plasma concentrations to counteract Ca2+--induced 395 muscle twitches, vasospasms, and glutamate-mediated neuronal excitement in eclamptic and 396 severely pre-eclamptic women (45–47). Moreover, the goal is to hinder cholinergic transmission 397 at the neuromuscular junction to stop or avoid convulsive episodes (46,47). 398 Under Pritchard method, patients receive an initial loading dose of 14g MgSO₄ . This is 399 implemented as 4g slow IV infusion using a 20% solution, which provides immediate 400 anticonvulsant activity lasting about 30 minutes. This is followed by a 10g intramuscular (IM) 401 injection using a 50% solution, extending the anticonvulsant effect for 3-4 hours. To maintain 402 therapeutic levels, a 5g IM dose is injected into alternating gluteal muscles every 4 hours for up to 403 24 hours (46,47). Eight hospitals stocked the 50% w/v MgSO₄ in 10 ml ampoules in compliance 404 with WHO requirements (48). However, one hospital only had 20% w/v MgSO₄, presenting a 405 significant clinical challenge. A 5g IM dose of 20% MgSO₄ requires 25 ml, exceeding the regular 406 injection volume of 10 ml for gluteal muscles from a 50% solution (19,49). Some hospital 407 pharmacists might have underestimated the health implication of substituting a 50% w/v MgSO₄ 408 solution with a 20% for IM doses. Such an excess volume may cause pain, drug leakage, 409 inflammation, and abscess formation (50,51). This issue, as highlighted by Babu et al. (2022) may 410 contribute to poor patient compliance with IM maintenance therapy (52). . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 23 411 At the sites, severe pre-eclamptic/eclamptics received six IM maintenance doses based on the 412 MgSO4 protocols evaluated. These amounted to cumulative doses of 44g MgSO 4 for each patient 413 in 24 hours as opposed to 40g reported in some literature (53). Despite high adherence to the 414 MgSO₄ guidelines, none of the hospitals had the capacity to monitor serum Mg²⁺ levels, relying 415 instead on urine output, respiratory rate, and patellar reflexes, a practice that may be insufficient 416 for preventing toxicity. Given the risk of accumulation in patients with impaired renal function, 417 dose adjustments based on weight or alternative regimens like the Dhaka regimen or a 12-hour 418 protocol proposed by Beyuo et al. ( 2022) may be safer options for facilities without laboratory 419 capacity (54–56). 420 The study had some drawbacks. For example, part of the data was collected by observing drug 421 protocols, drug shelves, and medicine trays. In addition, procedural data were gathered from 422 physicians, labor/maternity unit heads, and pharmacists rather than by watching actual procedures 423 being performed which might differ. Moreover, inaccurate records might have been captured in 424 labor registers, which could impact the quality of the data collected. Again, the study did not 425 include health centers, private clinics, or maternity homes since it was assumed that many HDP 426 patients would be directed to major hospitals because such smaller facilities were unable to handle 427 maternal complications or conduct caesarean surgeries when urgent deliveries were required. If 428 some HDPs were managed without referral, this would have an effect on the statistics that this 429 study projects. 430 Conclusions 431 The prevalence of HDP in the Bono Region of Ghana was 4.4%. Pre-eclampsia was the most 432 common HDP. Young parturient age, unemployment, primigravida and primiparity were the 433 predictors of pre-eclampsia/eclampsia. The extended-release oral nifedipine and IV hydralazine . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 24 434 were the main therapies for HDPs, especially for severe pre-eclamptic patients. Magnesium 435 sulfate protocols for pre-eclampsia/eclampsia conformed to standard regimen. The supply of 436 20% MgSO4 solutions for IM maintenance doses was inappropriate due to its larger injection 437 volumes that may be harmful to patients. Standardizing the concentration of magnesium sulfate 438 solutions for pre-eclampsia/eclampsia could optimize intramuscular dosing under Pritchard 439 regimen, improving treatment consistency. 440 Acknowledgments 441 We appreciate the Bono Regional Health Directorate and the medical directors or administrators 442 of all the hospitals for granting us permission to access hospital records for data. We also 443 appreciate the cooperation of midwives, doctors and pharmacists in the hospitals for providing 444 some information that was needed for this study. 445 446 References 447 1. WHO. Acceleration towards the sustainable development goal targets for maternal health 448 and child mortality. 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(which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 29 620 621 Supporting information 622 S1 Fig. Patients’ diagnoses 623 S1 Table. Sociodemographic data of women involved in the study 624 S2 Table. A comparison of hypertensive disorders with maternal sociodemographic 625 characteristics 626 S3 Table. Parturients’ factors and their association with hypertensive disorders (n=711). 627 Note: * (Fisher’s exact) 628 S4 Table. Regression analysis of the association between maternal sociodemographic data 629 with pre-eclampsia/eclampsia. aOR, adjusted odds ratio; cOR, crude odds ratio; CI, confidence 630 interval; p, probability 631 S5 Table. Antihypertensive medicines available in the hospitals for managing hypertension 632 in pregnancy. IV, intravenous 633 S6 Table. Usage of MgSO4 to manage pre-eclampsia/eclampsia by hospitals in Bono 634 Region. IM, Intramuscular; IV, Intravenous; MgSO4, Magnesium sulfate 635 636 S1_Fig.docx S1_Table.docx S2_Table.docx S3_Table.docx S4_Table.docx S5_Table.docx 637 S6_Table.docx S1 file_Dataset.xlsx 638 Competing interest 639 No conflict of interest is declared by authors 640 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint 30 641 Funding 642 We received no funding from any source. 643 644 Data availability statement 645 All relevant data are within the manuscript and its supporting information file attached 646 647 Authors’ contributions 648 Conceptualization: Francis Fordjour, Edward Tieru Dassah and Kwame Ohene Buabeng 649 Data curation: Francis Fordjour, Bernard Okyere, Kwadwo Addai-Darko 650 Data analysis: Francis Fordjour, Jonathan Boakye-Yiadom and Edward Tieru Dassah 651 Methodology: Francis Fordjour, Edward Tieru Dassah and Kwame Ohene Buabeng, 652 Mentorship & supervision: Edward Tieru Dassah and Kwame Ohene Buabeng, 653 Writing-original draft: Francis Fordjour, Bernard Okyere, Jonathan Boakye-Yiadom and 654 Edward Tieru Dassah 655 Writing-review & editing: Kwadwo Addai-Darko, Edward Tieru Dassah, and Kwame 656 Ohene Buabeng 657 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2025. ; https://doi.org/10.1101/2025.05.18.25327871doi: medRxiv preprint