review of literature on pregnancy induced hypertension in india

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• v.16(4); 2019 Apr

The incidence of pregnancy hypertension in India, Pakistan, Mozambique, and Nigeria: A prospective population-level analysis

Laura a. magee.

1 School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom

Sumedha Sharma

2 Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada

Hannah L. Nathan

Olalekan o. adetoro.

3 Olabisi Onabanjo University, Ago Iwoye, Ogun State, Nigeria

Mrutynjaya B. Bellad

4 Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India

Shivaprasad Goudar

Salécio e. macuacua.

5 Centro de Investigação em Saúde da Manhiça, Manhiça, Mozambique

Ashalata Mallapur

6 S Nijalingappa Medical College, Hanagal Shree Kumareshwar Hospital and Research Centre, Bagalkote, Karnataka, India

Rahat Qureshi

7 Centre of Excellence, Division of Woman and Child Health, Aga Khan University, Karachi, Pakistan

Esperança Sevene

John sotunsa.

8 Babcock University Teaching Hospital, Ilishan-Remo, Ogun State, Nigeria

Anifa Valá

Beth a. payne.

9 Centre for International Child Health, University of British Columbia, Vancouver, British Columbia, Canada

Marianne Vidler

10 Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada

Andrew H. Shennan

Zulfiqar a. bhutta, peter von dadelszen, associated data.

The data on which the manuscript is based are freely available without restrictions from the CLIP Trials Data Access Committee, that can be contacted at ac.cb.wc@TPME-ERP , as referenced on our website at https://PRE-EMPT.bcchr.ca . There is no pregnancy-specific repository for us to access, but once the primary publications for the CLIP trials are out, we will be depositing our data in the HDKQi repository at the Bill & Melinda Gates Foundation.

Most pregnancy hypertension estimates in less-developed countries are from cross-sectional hospital surveys and are considered overestimates. We estimated population-based rates by standardised methods in 27 intervention clusters of the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials.

Methods and findings

CLIP-eligible pregnant women identified in their homes or local primary health centres (2013–2017). Included here are women who had delivered by trial end and received a visit from a community health worker trained to provide supplementary hypertension-oriented care, including standardised blood pressure (BP) measurement. Hypertension (BP ≥ 140/90 mm Hg) was defined as chronic (first detected at <20 weeks gestation) or gestational (≥20 weeks); pre-eclampsia was gestational hypertension plus proteinuria or a pre-eclampsia-defining complication. A multi-level regression model compared hypertension rates and types between countries ( p < 0.05 considered significant). In 28,420 pregnancies studied, women were usually young (median age 23–28 years), parous (53.7%–77.3%), with singletons (≥97.5%), and enrolled at a median gestational age of 10.4 (India) to 25.9 weeks (Mozambique). Basic education varied (22.8% in Pakistan to 57.9% in India). Pregnancy hypertension incidence was lower in Pakistan (9.3%) than India (10.3%), Mozambique (10.9%), or Nigeria (10.2%) ( p = 0.001). Most hypertension was diastolic only (46.4% in India, 72.7% in Pakistan, 61.3% in Mozambique, and 63.3% in Nigeria). At first presentation with elevated BP, gestational hypertension was most common diagnosis (particularly in Mozambique [8.4%] versus India [6.9%], Pakistan [6.5%], and Nigeria [7.1%]; p < 0.001), followed by pre-eclampsia (India [3.8%], Nigeria [3.0%], Pakistan [2.4%], and Mozambique [2.3%]; p < 0.001) and chronic hypertension (especially in Mozambique [2.5%] and Nigeria [2.8%], compared with India [1.2%] and Pakistan [1.5%]; p < 0.001). Inclusion of additional diagnoses of hypertension and related complications, from household surveys or facility record review (unavailable in Nigeria), revealed higher hypertension incidence: 14.0% in India, 11.6% in Pakistan, and 16.8% in Mozambique; eclampsia was rare (<0.5%).

Conclusions

Pregnancy hypertension is common in less-developed settings. Most women in this study presented with gestational hypertension amenable to surveillance and timed delivery to improve outcomes.

Trial registration

This study is a secondary analysis of a clinical trial - ClinicalTrials.gov registration number {"type":"clinical-trial","attrs":{"text":"NCT01911494","term_id":"NCT01911494"}} NCT01911494 .

Laura Magee and colleagues present a survey of hypertension levels in pregnant women based on data from clinical trials in low and middle income countries.

Author summary

Why was this study done.

• High blood pressure in pregnancy is thought to occur in up to 1 in 10 pregnant women.
• Most information is from more-developed countries or from referral hospitals in less-developed countries, which is regarded to overestimate the occurrence of this condition.

What did the researchers do and find?

• As part of the Community-Level Interventions for Pre-eclampsia (CLIP) trials in 27 geographical clusters (India, Pakistan, Mozambique, and Nigeria; 2013–2017), we undertook standardised blood pressure measurement in 28,420 pregnancies, in women’s homes or their primary health centres.
• Hypertension occurred in about 10% of pregnancies by standardised measurement, usually based on elevation of only the bottom (diastolic) number and often diagnosed for the first time postpartum; rates were 2%–7% higher when diagnoses from clinical care were included.
• At first presentation with elevated blood pressure, most (7%–8%) hypertension was pregnancy-induced (‘gestational’) without other associated problems.

What do these findings mean?

• In our study countries, hypertension in pregnancy was more common than previously estimated.
• Most hypertension could only be measured with a blood pressure device, and not by using a cuff and palpation alone.
• Most women presented with gestational hypertension that is amenable to surveillance and timed delivery to decrease adverse outcomes for mothers and their offspring.
• Many women presented with hypertension only postpartum, highlighting the need for ongoing surveillance of maternal well-being after birth.

Introduction

The United Nations Sustainable Development Goal (SDG) 3.1 aims to reduce the global maternal mortality ratio to less than 70 per 100,000 live births by 2030 [ 1 ]. The SDGs aim to maintain the momentum of the Millennium Development Goals, which catalysed a global reduction in maternal deaths from approximately 390,000 in 1990 to 275,000 in 2015 [ 1 , 2 ]. The burden of maternal mortality remains disproportionately borne by women in less-developed countries, particularly in sub-Saharan Africa (66%, 201,000 deaths) and southern Asia (22%, 66,000 deaths) [ 3 ].

One of the leading causes of maternal death (and disability) worldwide is pregnancy hypertension [ 4 ]. Incidence estimates from less-developed countries have varied from 4.0% to 12.3% [ 4 – 9 ]. These estimates are based on facility-based cross-sectional cohort studies, which are likely to overestimate rates compared with population-based data. Thus, the true incidence is unknown. Adding further to these measurement challenges are a lack of access to quality antenatal care and blood pressure (BP) measurement, the lack of a standardised definition for pre-eclampsia, and variable quality and coverage of routine health information systems; for example, national demographic health surveys have reported that only half of women have a BP measurement during antenatal care in Mozambique (54.4%) [ 10 ], and although the corresponding figure in India is 89%, only half of women report receiving at least 4 antenatal care visits [ 11 ].

Pregnancy hypertension is classified into 3 major categories: pre-existing (chronic) hypertension, gestational hypertension, and pre-eclampsia (which includes eclampsia). In the World Health Organization (WHO) Multicountry Survey on Maternal and Newborn Health—a cross-sectional hospital-based survey of 313,030 women admitted to 357 health facilities in 29 countries across Africa, Asia, Latin America, and the Middle East—0.29% of women were reported to have chronic hypertension (range 0.21% [Africa] to 0.32% [Western Pacific]) [ 12 ], 2.2% pre-eclampsia (excluding eclampsia; range 1.4% [Middle East] to 3.9% [Africa]), and 0.28% eclampsia (range 0.14% [Western Pacific] to 0.55% [Africa]) [ 12 , 13 ]; gestational hypertension was excluded from the WHO multicountry survey estimates. Other published rates have varied considerably; in hospital-based retrospective or prospective studies of variable size, gestational hypertension has been reported to complicate 2%–3% of deliveries in Karachi, Pakistan [ 14 ], 6.6% in south India [ 15 ], and 28.9% in southwest Nigeria [ 16 , 17 ].

We sought to establish reliable estimates of pregnancy hypertension incidence and type in 4 less-developed settings in southern Asia (India and Pakistan) and sub-Saharan Africa (Mozambique and Nigeria), using BP data gathered in the community using a validated semi-automated BP device from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials ( {"type":"clinical-trial","attrs":{"text":"NCT01911494","term_id":"NCT01911494"}} NCT01911494 ) [ 18 ].

This is a secondary, planned analysis of data collected in the 4 countries and 27 intervention clusters of the CLIP cluster randomised controlled trials ( {"type":"clinical-trial","attrs":{"text":"NCT01911494","term_id":"NCT01911494"}} NCT01911494 ) [ 18 ], in India ( N = 6, Karnataka State), Pakistan ( N = 10, Sindh Province), Mozambique ( N = 6, Maputo and Gaza Provinces), and Nigeria ( N = 5, Ogun State). A STROBE checklist is provided ( S2 Table ).

In brief, pregnant women (aged 15–49 years in India, Pakistan, and Nigeria, and 12–49 years in Mozambique) were enrolled in the CLIP trials when they first declared their pregnancy and following informed consent. The CLIP intervention consisted of community engagement and community health worker (CHW)–provided mobile health-guided clinical assessment, initial treatment, and referral to facility. Surveillance data were collected by a separate surveillance team, by quarterly household surveys in Pakistan, 6-monthly household surveys in Mozambique and Nigeria, and a research registry of facility records in India. The primary outcome was a composite of maternal, fetal, and newborn mortality and major morbidity. The protocol has been published [ 18 ] and is included S1 Text , along with the statistical analysis plan ( S2 Text ). The trials were approved by the University of British Columbia Research Ethics Board (H12-03497) and within each country (MDC/IECHSR/2013-14/A, India; 2590-Obs-ERC-13, Pakistan; 219/CNBS/13, Mozambique; OOUTH/DA.326/T/1/, Nigeria).

The CLIP intervention was implemented in primarily rural areas of India (February 2014 to October 2016), Pakistan (February 2014 to December 2016), Nigeria (March 2014 to January 2016), and Mozambique (February 2015 to February 2017). Within each country, a potential cluster consisted of an established unit of the health system (i.e., primary health centre [PHC] in India, union council in Pakistan, administrative post in Mozambique, and local government area in Nigeria), consisting of all relevant villages and PHCs (other than in India, where the PHC defined the cluster) within each unit. Potential clusters were chosen by the local team (based on similar healthcare infrastructure, accessibility to the surveillance team, and the absence of conflicting concurrent research activity). A random sample was then chosen, with restricted, stratified central randomisation (according to population size and region) to the intervention or to control (usual care).

In intervention clusters, CHWs were trained to provide mobile health-guided visits—supplementary pregnancy hypertension-oriented antenatal and postpartum care at home (India, Pakistan, and Mozambique) or at a PHC (Nigeria). Women in control clusters received usual care, advocated by WHO as BP measurement (using the device available) and proteinuria testing at each antenatal care visit at primary or other health centres; in these settings, most women receive 1 such visit at PHCs, and few women receive 4. In none of the study countries did CHWs usually either manage pregnancy hypertension or carry with them BP measurement equipment or antihypertensive medication; further details of their training and usual duties are detailed in S3 Text .

The CLIP intervention visits were guided by a novel mobile health application provided on Android tablets—Pre-eclampsia Integrated Estimate of Risk on the Move (POM)—that provided step-by-step guidance for clinical assessment (including oximetry in Pakistan and Mozambique), input of clinical data, and decision support for initial triage, transport, and treatment of women identified with pregnancy hypertension or emergency medical conditions [ 19 ]. This management was based on prediction of adverse maternal outcome and stillbirth, derived from incorporation into POM of the miniPIERS predictive model in hypertensive pregnancy [ 20 ]; this is a demographics-, symptom-, and sign-based model for use in low-resource settings to identify the risk of adverse maternal outcome among women with pregnancy hypertension. Usability and feasibility testing supported experimental implementation into clinical care [ 21 ].

POM-guided clinical assessment consisted of (i) a visual scan and enquiry for evidence of an emergency condition that would warrant immediate referral (i.e., unconsciousness, stroke or seizure, significant vaginal bleeding, or lack of fetal movement in the preceding 12 hours); (ii) signs or symptoms suggestive of end-organ involvement of pre-eclampsia (i.e., maternal symptoms of headache or visual disturbances, chest pain or dyspnoea, epigastric or right upper quadrant abdominal pain, or vaginal bleeding with abdominal pain); (iii) BP measurement; (iv) measurement of dipstick proteinuria both during the first antenatal visit and at all visits at which the woman was hypertensive; and (v) blood oxygen saturation assessment, using an Android mobile-phone- or tablet-adapted pulse oximeter to further improve risk stratification (Mozambique and Pakistan only) [ 22 ]. Clinical assessments were recommended every 4 weeks until 28 weeks gestation, every 2 weeks from 28 to 35 weeks, weekly from 36 weeks until delivery, once within 24 hours of birth, and postnatally around postpartum days 3, 7, and 14; in Nigeria, visits were opportunistic when women attended the PHC.

BP was measured using a semi-automated oscillometric device, validated for use in pregnancy and pre-eclampsia (Microlife 3AS1-2) [ 23 ]. CHWs were trained to have women rest for 5 minutes and then measure BP in a standardised fashion, at least twice ( S3 Table ). All BP readings were manually entered into POM, which averaged them as the BP for that visit; the first and second readings were averaged unless they were more than 10 mm Hg different, in which case a third reading was requested and the second and third readings were averaged [ 24 ]. The POM device provided guidance for community-initiated treatment (i.e., methyldopa 750 mg for systolic BP [sBP] ≥ 160 mm Hg and intramuscular magnesium sulphate 10 g for miniPIERS score > 25%) and referral (within 24 hours for sBP ≥ 140 mm Hg, and within 4 hours for emergency conditions, sBP ≥ 160 mm Hg, or miniPIERS score > 25%) [ 19 ].

Hypertension was defined as sBP ≥ 140 mm Hg or diastolic BP (dBP) ≥ 90 mm Hg. All normotensive POM-guided visits were included until the woman was found to be hypertensive, if applicable. Hypertension was defined as chronic (first detected at <20 weeks gestation) or gestational (first detected at ≥20 weeks) [ 25 ]. The rates for pre-eclampsia (and eclampsia) were estimated among pregnancies of women who were assessed and normotensive at <20 weeks gestation or who were first assessed at ≥20 weeks; pre-eclampsia was defined as gestational hypertension with proteinuria or 1 or more relevant end-organ complications [ 25 ]. Eclampsia was defined as seizure associated with pregnancy hypertension and was considered as a form of pre-eclampsia (detailed definitions in S4 Table ).

The data entered on the POM devices from women in intervention clusters were synchronised and stored on Research Electronic Data Capture servers, and transferred regularly to the University of British Columbia CLIP Co-ordinating Centre in Vancouver.

Trial surveillance data (i.e., baseline characteristics, processes of care and delivery, and adverse maternal, perinatal, and neonatal outcomes) were based on maternal report and collected by an independent team of fieldworkers trained in household surveillance (Pakistan, Mozambique, and Nigeria) or were collected by review of facility records (India), initially on paper and then electronically using tablets. Surveillance occurred quarterly in Pakistan, 6-monthly in Mozambique, and prospectively in near real time via the Global Network for Women’s and Children’s Health Research’s Maternal Newborn Health Registry in India [ 26 ]. In Nigeria, trial surveillance data (which included extended baseline characteristics and outcomes) were not available as surveillance was suspended and the trial closed shortly after the pilot phase because of challenges identified in data entry from paper case report forms to the electronic database; of note, POM device data in Nigeria (and all CLIP countries) were entered directly into POM by the CHWs, a different team from those trained to conduct trial surveillance. Data management protocols ensured data security by encryption, data tracking through user identification numbers and audit trails, and effective data synchronisation between devices within the same study cluster and with the Research Electronic Data Capture server. For this analysis, we included pregnancies of women in intervention clusters who had received at least 1 POM-guided visit and who had delivered by trial end. We excluded pregnancies of women who were still on follow-up (i.e., undelivered) to avoid underestimation of hypertension incidence. Our focus was on the type of pregnancy hypertension at first presentation with elevated BP in the community, to provide data for clinicians to inform individual counselling and care; these data were derived from POM. Of additional interest was pregnancy hypertension incidence and type overall, to provide data for those responsible for planning resource allocation; these data were derived from both POM and trial surveillance that included information around the time of delivery.

The intervention clusters in each country were treated as 1 cohort for the purposes of our primary analysis comparing pregnancy hypertension epidemiology (i.e., incidence, type, and severity) between countries. In sensitivity analyses, hypertension incidence and type at presentation were evaluated (i) among all pregnancies of women who received POM-guided visits, regardless of delivery status (i.e., this analysis included women who were still undelivered at the end of the trial), (ii) following adjustment for baseline maternal characteristics (i.e., age, parity, and maternal basic education, except in Nigeria where data were not available), and (iii) following incorporation of trial surveillance data that included data and diagnoses from the household surveys and review of facility records. No adjustment was made for gestational age at first POM-guided care visit or total number of visits because the relationship between gestational age at a visit and probability of diagnosing hypertension is inconsistent, with a nadir of BP at approximately 20 weeks, and the predominance of hypertension at term gestational age [ 24 ]. Continuous data were summarised by mean and standard deviation or median and interquartile range, as appropriate, to avoid making assumptions about the distribution of the data. Categorical data were summarised by number and proportion. Pairwise country comparisons were made by chi-squared test and Wilcoxon signed rank test, as appropriate. Between-country comparisons were made by chi-squared test for categorical variables and Kruskal–Wallis test for continuous variables, as appropriate. Hypertension rates between countries were compared using logistic regression, adjusting for country. Additional explanatory analyses were undertaken to explore the basis of any between-country differences based on women’s baseline characteristics. Analyses were performed using R programming software (version 3.3.2). p < 0.05 was considered statistically significant.

Of the 44,794 pregnancies in CLIP intervention clusters, 12,211 (27.2%) did not receive at least 1 POM-guided visit, and 4,163 (9.3%) were not delivered by trial end, leaving 28,420 (63.4%) pregnancies for inclusion in this analysis ( Fig 1 ).

POM, Pre-eclampsia Integrated Estimate of Risk on the Move.

There were statistical differences between countries for all baseline pregnancy characteristics ( Table 1 ). At enrolment in CLIP, women in India and Mozambique were younger than were those in Pakistan and Nigeria, but the absolute differences were very small. About one-third of women were nulliparous, except in Pakistan, where the proportion was closer to one-fifth. Women in India were enrolled earlier, usually at the end of the first trimester, compared with enrolment predominantly in the second trimester in other countries, particularly in Mozambique. Rates of maternal basic education were low overall, particularly in Pakistan. There were more multiple pregnancies in Mozambique, but the proportion was still small (<3%). CLIP data did not include information about smoking, body mass index, or prior pre-eclampsia. In all countries, women who received 1 or more POM-guided visits and those who did not were similar at baseline, although median gestational age at enrolment in CLIP was 2–4 weeks earlier for the former than for the latter ( S5 Table ); information was unavailable in Nigeria (see Methods ).

Data are number (%) of pregnancies or median [IQR].

*The p -value was based on comparisons of all groups by Kruskal-Wallis test for continuous variables, and chi-square test for categorical variables, as appropriate.

† Maternal basic education is defined as ≥8 years of schooling (India), ≥5 years of schooling (Pakistan), or achievement of Grade 5 or above (Mozambique).

‡ Trial surveillance data was not available for Nigeria.

CLIP, Community-Level Interventions for Pre-eclampsia; GA, gestational age; POM, Pre-eclampsia Integrated Estimate of Risk on the Move.

In ≥98.5% of informative pregnancies, there was an antenatal POM-guided visit, usually within a few weeks of enrolment, other than in Nigeria, where there was a 3-month delay on average ( Table 1 ). As such, the first POM-guided visit occurred before 20 weeks gestation in most (73.4%) pregnancies in India, just under half (40.6%) in Pakistan, and a distinct minority (<20%) in Mozambique and Nigeria. In most pregnancies, there was a postpartum visit, other than in Nigeria. Given the median gestational age at delivery, the median number of POM-guided visits received by women was lower than the frequency recommended in the CLIP protocol, in India (i.e., 10 versus 14 recommended), Pakistan (i.e., 5 versus 11 recommended), and Mozambique (i.e., 6 versus 10 recommended); data were not available in Nigeria. At the majority of the 168,997 POM-guided visits in all countries, BP was measured, both antenatally and postpartum ( Table 2 ). As per the CLIP protocol, proteinuria was measured at >90% of the first antenatal visits, and 91.2%–96.7% of subsequent antenatal visits at which the woman was hypertensive, in all but Nigeria, where the proportion was lower (80.7%).

Data are number (%) of women.

*The p -value was based on comparisons of all groups by chi-squared test (only relevant for comparison of quality of visits).

† The CLIP protocol specified that proteinuria should be measured at the first CLIP visit, and then at subsequent visits at which the woman was hypertensive. In Nigeria, proteinuria was measured at many subsequent visits regardless of BP status (12,796/21,354, 59.9%).

BP, blood pressure; CLIP, Community-Level Interventions for Pre-eclampsia; POM, Pre-eclampsia Integrated Estimate of Risk on the Move.

Approximately 10% of pregnancies in each of the 4 countries were identified as hypertensive at a POM-guided visit ( Table 3 ). The incidence was highest in Mozambique and lowest in Pakistan. In most pregnancies, diagnostic criteria for hypertension were met based on isolated dBP ≥ 90 mm Hg, except in India, where the proportion was just under half. Few pregnancies (<10% in all but Mozambique) were hypertensive based only on isolated systolic hypertension. In few pregnancies overall was isolated diastolic hypertension later associated with systolic hypertension (i.e., 75/295 [29.8%] in India, 58/734 [10.3%] in Pakistan, 20/285 [8.6%] in Mozambique, and 34/457 [10.6%] in Nigeria, p < 0.001), other than in India, where women presented earlier and had significantly more BP assessments. At least 85% of identified hypertension was non-severe, least commonly in Nigeria.

Data are number (%) of women or median [IQR].

*The p -value was based on comparisons of all groups by Kruskal–Wallis test for continuous variables, and chi-squared test for categorical variables, as appropriate.

† Chronic hypertension incidence was estimated only among women who were assessed at <20 weeks gestation. Gestational hypertension and pre-eclampsia incidence were estimated among women who were previously assessed as normotensive at <20 weeks or assessed for the first time at ≥20 weeks. For complete definitions please see S3 Table .

‡ Not mutually exclusive.

‖ Unknown because GA at hypertension diagnosis not known.

dBP, diastolic blood pressure; GA, gestational age; sBP, systolic blood pressure; POM, Pre-eclampsia Integrated Estimate of Risk on the Move.

In most pregnancies, hypertension was diagnosed antenatally (particularly in India), in the mid-late third trimester ( Table 3 ). However, in a substantial proportion of pregnancies (approximately 40%), hypertension was first diagnosed by a POM-guided visit postpartum. This occurred despite virtually all such women having been confirmed to be normotensive antenatally, a median of under 2 weeks before delivery in all but Pakistan, where the last antenatal POM-guided visit was a median of 3 weeks before delivery. Postpartum hypertension was usually diagnosed within 7 days of delivery, except in India; there, the incidence of postpartum hypertension was lowest, and the timing of diagnosis was the most remote from delivery (i.e., median 10 days postpartum).

The incidence of chronic hypertension, reported only in pregnancies with an antenatal POM-guided visit at <20 weeks gestation, was lower in India (1.2%) and Pakistan (1.5%) compared with Mozambique (2.5%) and Nigeria (2.8%) ( Table 3 ). When hypertension appeared at ≥20 weeks gestation, gestational hypertension was most common, with a slightly higher rate in Mozambique (8.4%) than in the other countries (approximately 7%). Most hypertension was diagnosed antenatally in India and Mozambique, whereas about half was so diagnosed in Pakistan and Nigeria.

Pre-eclampsia incidence was similar in each of the 4 countries (2.3%–3.8% of women). Most cases were diagnosed based on a broad definition that did not mandate the presence of new proteinuria (see S3 Table for definitions). Approximately one-third of pregnancies with pre-eclampsia demonstrated new proteinuria (other than in Mozambique, where the rate was <10%), most women had relevant maternal symptoms, many had maternal signs (particularly in Nigeria), and few (<5%) had reduced fetal movement. Rarely, women first presented with eclampsia as their hypertensive disorder (1 case in India and 2 in Nigeria). Most pre-eclampsia was diagnosed antenatally and near term, with about two-thirds presenting at ≥34 weeks gestation; the exception was in India, where pre-eclampsia presented at a median of about 38 weeks. In the sensitivity analysis that adjusted for baseline maternal characteristics available, rates of hypertension by type remained different between countries ( S6 Table ).

In sensitivity analyses, inclusion of women who were undelivered at the end of the trial resulted in lower incidence estimates of hypertension in each country; this was true for any hypertension and for each type ( S6 Table ). Adjustment for maternal characteristics (age, parity, and education) revealed some differences of the 3 other countries from the comparator India ( S7 Table ): In Pakistan, hypertension incidence overall remained lower than in India (adjusted odds ratio [aOR] 0.75, 95% CI 0.67, 0.85; p < 0.001), and the observed lower rates of gestational hypertension (aOR 0.84, 95% CI 0.73, 0.97; p = 0.016) and pre-eclampsia (aOR 0.50, 95% CI 0.41, 0.63; p < 0.001) reached statistical significance. In Mozambique, results were similar to those from unadjusted analyses (not significant), except for a lower incidence of pre-eclampsia than in India (aOR 0.51, 95% CI 0.40, 0.66; p < 0.001). In Nigeria, adjustment for maternal age and parity (as education was unavailable) revealed a lower incidence of hypertension overall than in India (aOR 0.82, 95% CI 0.73, 0.92; p < 0.001), associated with a higher incidence of chronic hypertension (aOR 1.68, 95% CI 1.05, 2.70; p = 0.030) and a lower incidence of pre-eclampsia (aOR 0.52, 95% CI 0.40, 0.67; p < 0.001). Finally, when we included hypertension and relevant end-organ complications documented by trial surveillance until 6 weeks postpartum (except in Nigeria, where these data were unavailable), estimates of pregnancy hypertension incidence rose, and were 36% higher in India (14.0% versus 10.3%), 25% higher in Pakistan (11.6% versus 9.3%), and 54% higher in Mozambique (16.8% versus 10.9%) ( Table 4 ). Also, the relative proportions of types of hypertension differed because this approach also accounted for progression to pre-eclampsia/eclampsia at either subsequent POM-guided visits or according to trial surveillance. Overall, chronic hypertension was rare (<1.0% of pregnancies in all countries), gestational hypertension most common (6%–12% of pregnancies, highest in Mozambique), and pre-eclampsia intermediate in incidence (3%–6%, highest in India).

Data are number (%) of pregnancies.

*Trial surveillance data were not available for Nigeria.

† The p -value was based on comparisons of all groups by chi-squared test for categorical variables.

In almost 30,000 pregnancies from 27 CLIP intervention clusters in sub-Saharan Africa and southern Asia, use of standardised BP measurement revealed an incidence of pregnancy hypertension of approximately 10%. The rate was slightly lower in Pakistan, but the difference was not explained by between-country differences in measurable baseline maternal and pregnancy characteristics.

Our community-based incidence estimates of pregnancy hypertension types revealed that chronic hypertension was least common (approximately 1%–3% of pregnancies), gestational hypertension most common (approximately 6%–8%), and pre-eclampsia intermediate in incidence (2%–4%); eclampsia was rare (<1%) and was included within estimates of pre-eclampsia. Most pre-eclampsia diagnoses were based on a broad definition rather than proteinuria alone (present in up to 33% of pre-eclampsia pregnancies).

Most of the hypertension detected was solely diastolic, particularly when non-severe; this means that ascertainment of BP by palpation, which detects only systolic hypertension, would be both inadequate and inaccurate for clinical care in these settings. Most hypertension was diagnosed antenatally, usually in the mid-third trimester, supporting WHO recommendations for increased frequency of antenatal care visits and BP measurement approaching term gestation [ 27 ]. Importantly, a substantial number of women were first diagnosed with hypertension postpartum (despite being normotensive at antenatal CHW visits), emphasising the importance of post-delivery BP measurements in clinical care beyond the WHO recommendation to measure BP within the 24 hours after delivery [ 28 ].

The major strengths of our study are the population-based nature of recruitment, and standardised BP measurements, using a pregnancy-validated BP device [ 23 ]. We had a large sample size and evaluated women in 4 less-developed sub-Saharan and southern Asian countries. We estimated rates of chronic hypertension only among women who presented at <20 weeks gestation, an important consideration because most women in all but India first present for antenatal care beyond the first half of pregnancy, when chronic hypertension can be diagnosed. We evaluated women using repeated community BP measurements in the days after birth (which are often not performed even in well-resourced settings).

Limitations of this analysis include the fact that we had BP measurements by standardised methods only from community care, as facility care was not the focus of the CLIP trial. Our trial surveillance included documentation of hypertension and related complications from facility records and from women themselves; these data were included in a sensitivity analysis that suggested that our community estimates are conservative, possibly related to substantial numbers of women presenting with hypertension at the end of their pregnancy or around labour and delivery, at which point care did not include CHW-led community visits. CHWs were unable to perform their community assessments as frequently as specified in the CLIP protocol, particularly the weekly visits from 36 weeks until delivery; as such, we may have missed the onset of hypertension just before delivery, as suggested by the higher incidence of hypertension when we incorporated non-standardised clinical assessments of BP from trial surveillance. We were unable to adjust for gestational age at the initiation of POM-guided visits or for the number of visits, given the lack of a consistent relationship between gestational age at a visit and the probability of diagnosing hypertension; however, we will explore the relationship between the number of POM-guided visits and outcomes in future planned ‘dose–response’ analyses ( S2 Text ). We applied internationally agreed-upon definitions of pregnancy hypertension type based on gestational age at presentation [ 25 ]; we recognise that a limitation of this approach is that women who were assessed for the first time at ≥20 weeks gestation and found to be hypertensive could have been labelled as having gestational hypertension when in fact they had chronic hypertension, with/without a secondary cause such as renal disease. However, our approach is recognised to be the relevant clinical approach given the propensity of pre-eclampsia to progress, which must, as much as possible, be under observation. We were unable to include all end-organ complications of pre-eclampsia, assessed clinically or through laboratory tests; however, trial surveillance did incorporate those complications that would have been diagnosed and treated at facility. We had only basic maternal characteristics available for use in our adjusted analysis of hypertension rates and types by country. No information was available on past history of chronic hypertension, so our rates for chronic hypertension may be underestimated, particularly as many women first presented for antenatal care in the second half of pregnancy and so chronic hypertension could not be assessed directly. Of course, an estimate from any region cannot be assumed to be automatically generalisable to the whole country.

To our knowledge, this is the first study of pregnancy hypertension incidence and type in less-developed countries that is both population-based in terms of participants and standardised in terms of BP measurement, by positioning and use of a pregnancy-validated BP device [ 23 ]. Prior estimates from less-developed countries have varied from 4.0% to 12.3% and come primarily from facility-based cross-sectional cohort studies [ 4 – 9 ]. While such studies have been thought to overestimate pregnancy hypertension incidence, our data suggest that this may not be true. Our estimates are at least as high as those from more-developed settings [ 4 ] and still probably conservative given the impact of the addition of non-standardised clinical BP assessments made around the time of delivery and documented by trial surveillance.

Our estimate of chronic hypertension incidence resembles the 1%–2% from more-developed settings [ 4 ]. Our data are unique from less-developed settings as many women were evaluated at <20 weeks gestation.

As in well-resourced settings, gestational hypertension was the most common type of pregnancy hypertension in our study population (approximately 6%–8%). The rates we found are as high or higher than those published from facility-based retrospective or prospective cohort studies: 6.9% in India (compared with 6.6% published [ 15 ]), 6.5% in Pakistan (versus 1.7% published [ 14 ]), and 7.1% in Nigeria (compared with highly variable estimates from 1.3% [ 17 ] to 28.9% [ 16 ]); we identified no comparable published data in Mozambique. Of note, the median gestational age at enrolment in Mozambique and Nigeria was over 20 weeks; although it is possible that some cases of gestational hypertension were actually cases of chronic hypertension, the incidence of gestational hypertension in Mozambique and Nigeria was similar to that in India, where the median gestational age of enrolment was 13 weeks.

The incidence of pre-eclampsia in our study was similar to published rates of 2%–4% in more-developed countries [ 4 ], but slightly higher than rates previously documented in our study countries: 3.8% in India (versus 2.0% published [ 12 ]), 2.4% in Pakistan (versus 1.2% published [ 12 ]), and 3.0% in Nigeria (versus 2.3%–4.2% [ 12 , 17 , 29 ]); there were no comparable published data in Mozambique. Few women presented with eclampsia during community-based visits. The incidence of pre-eclampsia was lower than that of gestational hypertension, despite the broad definition of pre-eclampsia used in the study (i.e., without mandatory proteinuria).

A novel finding of this study is the high proportion of women diagnosed with hypertension based on dBP alone, and the fact that most did not go on to develop systolic hypertension at subsequent POM-guided visits. While the pregnancy hypertension literature to date has focused on dBP as a diagnostic criterion [ 30 ], this practice has been based on the greater susceptibility of sBP to environmental influences, rather than a regard for dBP being more important. However, outside pregnancy, high isolated dBP is characteristic of hypertension in the young [ 31 ] (as in our population), among whom it is the measure associated with elevated cardiovascular risk; it is in older populations that this association is assumed by systolic hypertension [ 31 ].

Finally, we have documented high rates of new postpartum hypertension (approximately 20%–45% of all cases of hypertension) based on a median of 2 postpartum CHW-led community visits and normal BP at antenatal visits. Comparable rates in either less- or more-developed countries are unknown, but in the latter, a rate of 2% has been estimated during the period prior to hospital discharge [ 32 , 33 ].

CHWs can measure BP and respond to hypertension; this has implications beyond maternity care to the broader SDG agenda related to non-communicable diseases [ 1 ]. Pregnancy hypertension is at least as common in less-developed countries as it is in more-developed. During active community surveillance of antenatal BP, most women present with non-severe elevations of BP due to gestational hypertension. As such, the severity and type of hypertension are amendable to intervention, by antihypertensive therapy [ 34 ] or timed delivery to optimise outcomes, particularly where there is limited capacity for the healthcare infrastructure to respond to obstetric emergencies. Future research should address, in particular, postnatal BP measurement and management.

Supporting information

Acknowledgments.

We wish to thank all the women who participated in the CLIP trials, the CHWs committed to their care, and members of the CLIP Study Group, particularly Akinmade Adepoju, Imran Ahmed, Jeffrey Bone, Umesh Charantimath, Zahra Hoodbhoy, Amjad Hussain, Geetanjali Katageri, Jing Li, Amit Revankar, Charfudin Sacoor, Sana Sheikh, and Domena K. Tu.

Abbreviations

Funding statement.

This study was funded by the University of British Columbia, a grantee of the Bill & Melinda Gates Foundation, through the PRE-EMPT initiative (grant number OPP1017337). The originating funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Data Availability

• Open access
• Published: 10 May 2023

Association between iron-folic acid supplementation and pregnancy-induced hypertension among pregnant women in public hospitals, Wolaita Sodo, Ethiopia 2021: a case- control study

• Abiyot Wolie Asres 1 ,
• Serawit Samuel 1 ,
• Wakgari Binu Daga 2 ,
• Atsede Tena 3 ,
• Afework Alemu 4 ,
• Shimelash Bitew Workie 1 ,
• Mihiretu Alemayehu 3 &
• Habtamu Messel 5  

BMC Public Health volume  23 , Article number:  843 ( 2023 ) Cite this article

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Pregnancy-induced hypertension is the new onset of high blood pressure after 20 weeks of gestation in women with previously normal blood pressure. To the best of our knowledge, no study has been conducted in our country to investigate the association between this pregnancy problem and iron-folic acid supplementation. The aim of this study was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension (PIH) in pregnant women at public hospitals in the Wolaita Sodo zone.

An institution-based case–control study was conducted among pregnant women who visited public hospitals in the Wolaita Sodo zone from March 3, 2022, to August 30, 2022. A consecutive sampling method was used to select the study participants. The total sample size was 492, of which 164 were cases and 328 were controls. The data were collected by conducting face-to-face interviews and measurements. The data were entered into EpiData version 4.6 and exported to STATA 14 for analysis. Those variables with a p -value less than 0.05 were considered statistically significant. Descriptive statistics and odds ratios were presented using texts, tables, and figures.

A total of 471 women participated in this study, yielding a response rate of 96%. The cases had a mean age of 25 ± 4.43, while the controls had a mean age of 25 ± 3.99. The mean age at first pregnancy among cases was 20 ± 2.82 and among controls was 20 ± 2.97. The average number of deliveries for cases and controls was 1.97 ± 1.41 and 1.95 ± 1.38, respectively. There is no significant association between iron-folic acid supplementation and PIH. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it (AOR = 3.65; 95% CI: 1.0–12.9). Eating kocho (AOR = 14.4; 95% CI: 1.2–16.7) was positively associated with PIH.

Conclusions

There is no association between iron-folic acid supplementation during pregnancy and pregnancy-induced hypertension. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it. There is an association between kocho consumption and PIH. More research should be done using stronger designs.

Peer Review reports

Pregnancy-induced hypertension is the new onset of high blood pressure after 20 weeks of gestation in women with previously normal blood pressure [ 1 ]. According to a study conducted by the World Health Organization (WHO) from 2003–2009, the leading causes of maternal death were hemorrhage (27·1%), pregnancy-induced hypertension (14·0%) and sepsis (10·7%). These were responsible for more than half of all maternal deaths worldwide [ 2 ]. Pregnancy-induced hypertension (PIH) is the most common medical complication of pregnancy, with an incidence of between 5 and 10%. The WHO estimates that at least one woman dies every 7 min from a complication of PIH [ 3 ]. The incidence of PIH increased from 16.30 million to 18.08 million globally, with a total increase of 10.92% from 1990 to 2019 [ 4 ].

The burden of PIH is high in Africa, with one in 10 pregnancies affected. The burden is significantly higher in Central and Western Africa [ 5 ]. Sub-Saharan Africa accounted for approximately 86% of the estimated global maternal deaths in 2017 [ 6 ]. During the ten-year period (2006–2015), there was an increase in the number of maternal deaths due to direct causes of pregnancy [ 7 ].

The maternal mortality rate in Ethiopia declined from 5.51% to 4.98% from 2014 to 2017, respectively. Nevertheless, maternal mortality due to PIH has increased [ 8 , 9 ]. Obstetric factors were directly responsible for 51 (86%) of all maternal deaths in Ethiopia. The primary direct causes of maternal mortality in Ethiopia were hemorrhage (45%), PIH (23%), and obstructed labor (18%). Among PIHs, preeclampsia was the most common type in the country [ 10 , 11 , 12 , 13 ].

Factors associated with PIH were: primigravida, extreme age, early gestational age, twin pregnancy, gravidity, long inter-pregnancy intervals, chronic hypertension, history of diabetes, multiple pregnancies, obesity, smoking, socioeconomic level, and diet [ 14 , 15 , 16 , 17 , 18 , 19 ]. Anemia and coffee intake during pregnancy are risk factors for the development of PIH [ 20 ]. Similarly, the level of iron was significantly higher in the PIH groups than in the control groups [ 21 ]. Antioxidant supplementation was associated with better maternal and perinatal outcomes than iron and folic acid supplementation alone [ 22 ]. The consumption of seafood was inversely associated with the odds of developing PIH [ 23 ]. PIH was less frequent in women who ate received iron and folic acid supplements [ 24 ]. Maternal ferritin concentration is primarily a reflection of maternal iron status, and a high level is associated with unfavorable outcomes. This indicates the need for further study of routine iron-folic acid supplementation in pregnant women [ 25 ].

The potential harmful effects of iron-folic acid were not carefully debated in regards to its effectiveness. Even if iron-folic acid is beneficial for neonatal or maternal outcomes, it is associated with glucose impairment and pregnancy-induced hypertension in mid-pregnancy [ 26 ]. High hemoglobin levels in women who took iron-folic acid supplements were associated with an increased risk of PIH [ 27 ]. Its supplementation before 16 weeks of gestational age was significantly associated with an increased risk of developing PIH [ 28 ]. But there was no association between the occurrence of PIH and the timing of iron-folic acid (IFA) supplementation. Early (< 28 weeks) and late (≥ 28 weeks) onset or start of iron-folic acid supplementation, on the other hand, was found to be protective [ 29 , 30 ]. Women in the lowest iron quartile had a 2.2-fold increase in PIH risk compared to women in the highest quartile [ 31 ]. In India, women who had a diet that was sufficiently varied and supplemented with iron and folic acid throughout pregnancy experienced fewer PIH symptoms. PIH symptoms were 36% lower in mothers who took iron-folic acid supplements for at least 90 days during their previous pregnancy [ 32 ].

A study showed that serum ferritin and serum iron were higher in PIH women [ 33 ]. The serum iron level has a direct correlation with the level of blood pressure, concentration of total hemoglobin, and serum iron [ 34 , 35 ]. Iron supplementation during pregnancy may have resulted in iron overload, which may have resulted in oxidative stress and endothelial dysfunction in the patients [ 36 ]. In contrast, there was no significant difference between PIH and serum iron concentrations [ 37 ].

PIH can be avoided through early detection and eating vegetables and fruits during pregnancy. The WHO highly suggests that pregnant women take daily oral iron and folic acid supplements to prevent maternal anemia, puerperal sepsis, low birth weight, and premature birth. Iron-folic acid should be started as soon as possible to prevent neural tube defects [ 38 ]. It was found that iron-folic acid supplementation is recommended for the benefit of the fetus and herself, but the prevalence of PIH is increasing, unlike other complications during pregnancy. Most factors in PIH were assessed using cross-sectional studies, which could not show a cause-and-effect relationship. Hence, the association between iron-folic acid supplementation and pregnancy-induced hypertension is not clear yet. Furthermore, to the best of our knowledge, there is no study done in Ethiopia on this association. Therefore, the aim of this study was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension among pregnant women.

Study design and settings

The aim of this study was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension among pregnant women in the public hospitals of Wolaita Sodo zone. An institution-based, unmatched case–control study was conducted among pregnant women attending ANC and admitted for delivery in obstetrics and gynecology departments. The study was conducted in the four public hospitals of Wolaita Sodo zone in southern Ethiopia from March 3, 2022, to August 30, 2022. The Southern Nation Nationalities and Peoples Regional State (SNNPR) is one of the ten regions that has a wide variety of nations and nationalities with different cultures, languages, lifestyles, weather conditions, topography, habitats, and other natural phenomena. The region has 16 zones, of which the Wolaita Sodo zone is one. Wolaita Sodo town is found in the southern direction of Addis Ababa (the capital city of Ethiopia) and in the southwest direction of Hawassa, about 329 and 151 km apart, respectively.

There are about eight governmental hospitals and two private hospitals in the Wolita Sodo zone. They include Wolaita Sodo University Comprehensive Specialized Hospital (WSUCSH), Bodity, Bitena, Bele, Bombe, Gesuba, Humbo, and Kindo Halale primary hospitals. The Wolaita Sodo University College of Health Science and Medicine is located in Wolaita Sodo town, which is 151 km west of Hawassa and 329 km south of Addis Ababa.

Case definition

Cases are defined as pregnant women whose blood pressure was greater than or equal to 140/90 mmHg in two separate readings taken 4 h apart [ 1 ]. They were diagnosed and confirmed by obstetrics and gynecology physicians. Controls are defined as pregnant women in the same hospitals whose blood pressure is less than 140/90 mmHg after 20 weeks of gestation. During the study period, cases and controls were identified through record review and after physician diagnosis in ANC clinics and obstetrics and gynecology wards. The diagnosis includes history-taking, clinical manifestations, a physical examination, and laboratory tests.

The source populations were pregnant women, both cases and controls, who attended ANC and were admitted for delivery in public hospitals in the Wolaita Sodo zone. The study population consisted of pregnant women who fulfilled the eligibility criteria. These were both cases and controls who attended ANC and were admitted for delivery in the selected hospitals during the study period. Consecutively chosen pregnant women, both cases and controls, in the selected hospitals during that study period were the sampled populations.

Inclusion and exclusion criteria

Women who attended ANC and were admitted for delivery and had a blood pressure readings greater than or equal to 140/90 mmHg or had a blood pressure of less than 140/90 mmHg after 20 weeks of gestation were included in this study. The study excluded severely ill pregnant women.

Sample size determination

The sample size was calculated using OpenEpi version 2.3 statistical software by assuming a proportion of cases exposed of 13%, a minimum detectable odds ratio among controls of 2.14 [ 28 ], a case-to-control ratio of 1: 2, a significant level of 95%, and a power of 80%. The sample size was 447. With a 10% non-response rate, the total sample size was 492 people, with 164 cases and 328 controls.

Sampling procedures

The four hospitals—Wolaita Sodo University Comprehensive Specialty Hospital (WSUCSH), Bitena, Bodity, and Humbo Primary Hospitals—were selected due to their high patient flow rates. The cases that fulfilled the inclusion criteria were selected using the consecutive sampling method until the required sample size was attained. Then the next two immediate corresponding controls were also selected consecutively on the same day in the ANC unit and labor wards (Fig.  1 ).

Sampling procedure to select the women in Wolaita Sodo zone public hospitals

Instruments (Questionnaire)

The data were collected through measurements, reviewing records, and face-to-face interviews using a pretested questionnaire. The measurements included blood pressure, weight, height, and urine from the women. The women were interviewed about their socio-demographic characteristics, obstetric factors, and behavioral factors by trained and experienced health professionals immediately before and after ANC and delivery services. A questionnaire was prepared by reviewing different pieces of literature that were similar to the current study [ 10 , 20 , 24 , 25 , 27 , 35 ]. Then the questionnaire was changed from English to Amharic and back-translated to English to check its consistency. The questionnaire was pretested on 5% of the sampled pregnant women.

Laboratory measurements and individuals

Twelve health professionals—eight BSc midwives and four MPH health professionals—were recruited as data collectors and supervisors, respectively. There were two trained data collectors for each hospital. The trained laboratory technicians measured proteinuria and hemoglobin levels.

The proteinuria was measured using a dipstick test. Urine specimens for proteinuria assessment were obtained from spot urine samples collected from pregnant women who attended ANC. The health care providers used a dipstick test with a color-sensitive pad. The color changes on the dipstick indicated the women's levels of protein in the urine.

Hemoglobin levels were determined using an automated hematology analyzer machine. Blood samples were drawn from the women's veins on the inside of their elbows. Needles were inserted into the veins, and the blood samples were collected using airtight vials. The blood samples were put into the automated hematology analyzer machine. Then hemoglobin levels were determined from these blood samples using this machine. The hemoglobin levels were categorized as >  = 11.0 mg/dl and < 11.0 mg/dl [ 39 ].

Data quality management

Training was given for data collectors and supervisors about two days before data collection. A clear explanation of the purpose of the study was provided to the respondents at the beginning of the interview. Supervisors and the principal investigator provided close supervision. The data from each respondent was checked for completeness, clarity, consistency, and accuracy by the data collectors, supervisors, and the principal investigator.

Statistical analysis

After data collection, the data were coded and entered using Epidata version 4.6 software. The entered data was then transformed into the STATA 14 version. Descriptive statistics like frequencies, percentages, means, and standard deviations were done. The association between pregnancy-induced hypertension and each variable was checked using bivariate logistic regression. Variables with a p -value less than 0.25 in the bivariate logistic regression were entered into multivariable logistic analysis, and those variables with a p -value of less than 0.05 in multivariate logistic regression were considered statistically associated factors. Text, tables, and figures were used to present the findings.

Socio-demographic characteristics

A total of 471 women participated in this study. The response rate was 96%. The cases had a mean age of 25 ± 4.43, while the controls had a mean age of 25 ± 3.99. The mean age at first pregnancy among cases was 20 ± 2.82 and among controls was 20 ± 2.97. The average number of deliveries for cases and controls was 1.97 ± 1.41 and 1.95 ± 1.38, respectively. About 153 (97.5%) of cases and 304 (96.8%) of controls were married. Regarding educational status, 12 (7.6%) of the cases and 11 (3.5%) of the controls could not read or write. Similarly, 79 (50.3%) of cases and 136 (43.3%) of controls were housewives. More than half (51.0%) of the cases and 198 (63.0%) of the controls were from urban residences (Table 1 ).

Obstetric and gynecological factors

About 100 (63.7%) of the cases and 225 (71.7%) of the controls were multigravida, and 9 (5.7%) of the cases and 11 (3.5%) controls had multiple pregnancies (Table 2 ).

Iron-folic acid supplementation related factors

One hundred thirty (82.8%) of the cases and 252 (80.2%) of the controls had taken iron during their pregnancies. After 16 weeks of gestation, 113 (86.9%) of the cases and 228 (90.5%) of the controls began their first dose of iron and folic acid supplementation. In terms of hemoglobin levels, 115 (73.2%) cases and 211 (67.2%) controls had levels greater than or equal to 11.0 g/dl. Only 42 (26.8%) cases and 103 (32.8%) controls had hemoglobin levels below the normal range (Table 3 ).

Behavioral factors

We have also assessed the behavioral and nutritional histories of the women who consumed during their pregnancies. Most of these nutrients are sources of iron. Among the commonly known sources of iron are teff (Eragrostis tef), animal products, cereals, and fish. Based on this study, 45 (28.7%) of cases and 112 (35.6%) of the controls ate injera that was prepared from teff [ 40 ]. Similarly, 78 (49.7%) of cases and 138 (43.9%) of controls consumed sweet foods or soft drinks [ 41 ] during this pregnancy (Table 4 ).

Association of iron supplementation and PIH

We used logistic regression analysis to identify factors associated with pregnancy-induced hypertension. Based on this, about nine variables were eligible for multivariable logistic regression analysis. There is no association between iron-folic acid supplementation and PIH. Even if our main objective was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension, we also assessed other dietary factors that could be sources of iron. Hence, hemoglobin levels and the consumption of kocho or bulla were found to be significantly associated with pregnancy-induced hypertension. The odds of PIH was 3.65 (1.0–12.9) times higher among women with a hemoglobin level >  = 11.0 mg/dl as compared with women whose hemoglobin level was less than 11.0 mg/dl (Table 5 ).

Pregnant women with high hemoglobin levels had higher odds of pregnancy-induced hypertension as compared to controls. The finding of this study was in line with a study conducted in Iran [ 27 ]. According to the study conducted in Iran, a high hemoglobin level in the first trimester was a risk factor for pregnancy-induced hypertension. The current finding is also consistent with the study conducted in Arba Minch and Abbottabad [ 34 , 42 ]. Hemoglobin determines the viscosity of blood. According to various studies, systolic and diastolic blood pressure both increase as hemoglobin levels rise [ 43 , 44 ]. An increase in free hemoglobin contents results in vasoconstriction, which leads to the development of PIH [ 45 ]. In pregnancy-induced hypertension, a drop in intravascular volume and a rise in tissue edema were caused by the loss of serum protein and an increase in capillary endothelial permeability [ 46 ]. Any organ, including the liver, brain, and lungs, could be affected. The blood volume reduction can cause the maternal hemoglobin concentration to rise [ 47 ]. However, the current finding contradicts a study conducted in India [ 32 ]. The possible explanation might be that the sample size in the Indian study was very small, which might have had a small effect. In addition to this, the study design was cross-sectional as compared with the current study, which did not show the cause-effect relationship as a case–control study. Furthermore, the study populations were different between the two studies. The current study's population included all pregnant women of any age and gestational age. It is found that pregnant women who later develop PIH have considerably higher levels of hemoglobin, hematocrit, serum iron, serum ferritin, and transferrin saturation [ 48 ]. In the PIH group, the platelet indices were lower, and the serum iron levels were higher [ 49 ].

In this study, there was no association between pregnancy-induced hypertension and iron-folic acid supplementation. It is consistent with a Thailand study, which found that taking iron and folic acid supplements late in pregnancy has no effect on pregnancy-induced hypertension. But, according to this study, early initiation of iron-folic acid supplementation before 16 weeks of pregnancy dramatically raised the risk of developing PIH [ 27 ]. This variation may be due to the fact that the time of initiation was early in pregnancy, whereas in the current study we assessed the association among pregnant women irrespective of gestational age or anemia status. Similarly, women who use high-dose folic acid supplements before pregnancy and through mid-pregnancy may be at increased risk for high blood pressure [ 50 ]. This finding is contrary to a study conducted in Poland. According to that study, PIH risk was 2.19 times higher in women in the lowest iron quartile (801.20 g/L) compared to those in the highest (> 1211.75 g/L) iron quartile [ 31 ]. The rise in blood iron observed in patients with PIH appears to be caused by a persistent, clinically undetectable hemolytic response. In addition to this, supplementing women with folic acid and multivitamins that contain folic acid rather than folic acid alone throughout pregnancy considerably lowers the incidence of PIH [ 29 , 30 ]. The possible reasons might be due to the differences between the study designs.

We have also assessed the association between pregnancy-induced hypertension and other nutritional-related factors. Based on this, there was another nutrient that was assessed in this study called kocho or bulla, which is one of the well-known and commonly consumed cultural foods in the study area. According to previous studies, iron is one of its constituents. There is a strong association between kocho or bulla consumption and PIH. Pregnant women who consumed bulla or kocho were 14.4 (1.2–16.7) times more likely to develop pregnancy-induced hypertension as compared with control groups [ 51 ]. This result seems to recommend that pregnant women avoid using bulla or kocho during their pregnancy, but this is the first study assessing this food and PIH. We were unable to obtain studies on the preceding or their mechanisms of action. We could not get any justification from previous literature about the effects of kocho or bulla on pregnancy-induced hypertension. Hence, it needs further study with regard to this association. We have also assessed nutrients that are rich in iron, like teff, but they had no association with pregnancy-induced hypertension.

The strength of this study is that, to the best of our knowledge, it is the first study of its kind in our country. But this study did not differentiate between the specific type of pregnancy-induced hypertension and its association with iron-folic acid supplementation. As a limitation, there might be respondents' recall biases regarding the number of iron and folic acid tablets they took, the total number of weeks they took the tablets, and the starting time of tablet taking. Some women might also hide the truth about whether they took the tablets completely or left them after taking them from the health institutions. This intern might affect the true association.

There is no association between iron-folic acid supplementation and pregnancy-induced hypertension. However, pregnant women with high hemoglobin levels had a higher risk of developing pregnancy-induced hypertension than those who did not. The concentration of iron-folic acid has a direct relationship with hemoglobin levels. Before giving iron and folic acid supplements to pregnant women, it is crucial to assess their iron status because they may have more detrimental consequences than good ones. All pregnant women should have their hemoglobin levels measured as a routine task during their first visit. Strong designs like randomized clinical trials or meta-analyses should be carried out with a large sample size.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Antenatal Care

Adjusted Odds Ratio

Body Mass Index

Blood Pressure

Diastolic Blood Pressure

Diabetes Mellitus

Ethiopian Demographic and Health Statistics

Gestational Age

Hypertension Disorder of Pregnancy

Health Professionals Education Partnership Initiative

Hypertension

Iron Folic Acid

Multiple Micronutrients

Pregnancy Induced Hypertension

Systolic Blood Pressure

Southern Nation Nationalities

Wolaita Sodo University Teaching and Comprehensive Specialized Hospital

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Acknowledgements

First of all, we thank you the study participants and data collectors. We would like to thank Health Professionals Education Partnership Initiative and Wolaita Sodo University.

This research work was supported by the Health Professionals Education Partnership Initiative Ethiopia with grant number R25TW011214.

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Department of Epidemiology and Biostatistics, School of Public Health, Wolaita Sodo University, Wolaita Sodo, Ethiopia

Abiyot Wolie Asres, Serawit Samuel & Shimelash Bitew Workie

Department of Reproductive Health and Nutrition, School of Public Health, Wolaita Sodo University, Wolaita Sodo, Ethiopia

Wakgari Binu Daga

School of Public Health, Wolaita Sodo University, Wolaita Sodo, Ethiopia

Atsede Tena & Mihiretu Alemayehu

Department of Pediatrics, School of Medicine, Wolaita Sodo University, Wolaita Sodo, Ethiopia

Afework Alemu

Health Professionals Education Partnership Initiative Project Office, Addis Ababa University, Addis Ababa, Ethiopia

Habtamu Messel

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AWA, AT, SBW, SS, AT & AA: participated in conception, data curation, formal analysis, investigation, funding acquisition, methodology, project administration, software, supervision, validation, visualization, writing-original draft preparation, writing -review & editing. AWA, WBD, SS, MA, HM, contributed to supervision, validation, visualization, writing -review & editing. All authors read and approved this manuscript submission.

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Correspondence to Abiyot Wolie Asres .

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The study was approved by Wolaita Sodo University Institution Review Board with ethical reference number of CRCSD 49/02/2014. Informed consent was obtained from all study participants and the study was carried out in accordance with relevant guidelines and regulations. Confidentiality and privacy of the respondents’ responses were maintained during data collection, analysis, and reporting of the findings.

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Asres, A.W., Samuel, S., Daga, W.B. et al. Association between iron-folic acid supplementation and pregnancy-induced hypertension among pregnant women in public hospitals, Wolaita Sodo, Ethiopia 2021: a case- control study. BMC Public Health 23 , 843 (2023). https://doi.org/10.1186/s12889-023-15794-6

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Received : 09 December 2022

Accepted : 03 May 2023

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DOI : https://doi.org/10.1186/s12889-023-15794-6

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Prevalence of hypertensive disorders of pregnancy and its maternal outcome in a tertiary care hospital, Salem, Tamil Nadu, India

• Subha Sivagami Sengodan Department of Obstetrics and Gynecology, Government Mohankumaramangalam Medical College Hospital, Salem, Tamil Nadu, India
• Sreeprathi N. Department of Obstetrics and Gynecology, Government Mohankumaramangalam Medical College Hospital, Salem, Tamil Nadu, India

Background: Hypertensive disorders complicate 5-10% of all pregnancies and together forms the deadly triad- along with hemorrhage and heart disease that contributes greatly to maternal morbidity and mortality. Objective of this study was to determine the prevalence of hypertensive disorders of pregnancy and its maternal complications in patients attending obstetrics and gynaecology department, Government Mohan Kumaramangalam Medical College Hospital, Salem.

Methods: This is a prospective study conducted from August 2018 to July 2019 in the department of obstetrics and gynaecology. Patients diagnosed with hypertensive disorders of pregnancy was evaluated and data were collected.

Results: A total of 19,383 pregnant women visited obstetrics and gynaecology department over a period of one year, out of which 2028 were diagnosed with hypertensive disorders of pregnancy. Hence the prevalence of hypertensive disorders in pregnancy is 10.4%. Among 2028 hypertensive disorder cases, Gestational hypertension were 962 cases (47.4%), pre-eclampsia 661 cases (32.6%), chronic hypertension 166 cases (8.2%) and pre-eclampsia superimposed on chronic hypertension 239 cases (11.8%). The prevalence was highest among primigravida (54%) compared to multigravida (46%). Hypertensive disorders were highest among the age group of 18-22 years in our study. Most common maternal complication in our study was HELLP syndrome.

Conclusions: Prevalence of hypertensive disorders was high in our study. Early detection and timely intervention decrease the maternal complications.

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