Bridging the gaps in knowledge, attitudes and practices on pre-eclampsia: key insights for improving maternal and neonatal healthcare in developing countries

Introduction

Hypertensive disorders of pregnancy (HDP) pose a significant yet often overlooked threat, claiming a substantial number of maternal and fetal lives worldwide. HDP is one of the three leading causes of maternal morbidity and mortality worldwide, responsible for 27 800 deaths in women of childbearing age in 2019.1 In sub-Saharan Africa, HDPs were the second leading cause of maternal mortality by 22.1%, followed by obstetric haemorrhage by 28.8% in 2020.2 Pre-eclampsia stands as a well-recognised medical condition within this disease spectrum, representing one of the most prevalent gestational complications accounting for approximately 2%–15% of all pregnancies.3 It is a multisystem disorder diagnosed after 20 weeks of pregnancy, lasting up to 6 weeks post partum, characterised by high blood pressure (≥140/90 mm Hg) and increased proteinuria (≥0.3 g/24 hours) in a previous normotensive woman. It may involve neurological complications such as seizures, altered mental status, blindness, stroke, clonus, severe headaches and persistent visual scotomata. Additionally, it can present with elevated liver enzymes indicating potential liver damage, with or without epigastric pain, pulmonary oedema, renal impairment and haematological issues like thrombocytopaenia, disseminated intravascular coagulation and haemolysis.4 5

Despite clinicians’ familiarity with the signs and symptoms of pre-eclampsia, early diagnosis of this condition is challenging. The complexity of pre-eclampsia often leads to rapid deterioration without prior warning, complicating efforts for early detection and intervention. This unpredictability of pre-eclampsia might result in significantly worse outcomes for patients and an increased risk of severe complications. Although pre-eclampsia cannot be entirely prevented, timely detection and appropriate management are important in mitigating its severity and improving patient outcomes.

Burden of pre-eclampsia, epidemiology, risk factors and complications

Pre-eclampsia is the second leading cause of direct maternal death in low-income and middle-income countries (LMICs), where access to and quality of antenatal and intrapartum care are limited. This condition affects 2%–15% of all pregnancies globally, with an average prevalence rate of approximately 4.6%, which varies widely from regions, such as 1.0% in the eastern Mediterranean and 5.6% in Africa.3 6 Globally, the condition was estimated to cause directly maternal deaths of 70 000, meanwhile in sub-Saharan Africa, the condition contributed about 56% and Southern Asia for 85% of the global burden.7 In sub-Saharan Africa, the prevalence of pre-eclampsia has been reported to be high, as up to 16%.4 A study conducted in the Central region of Ghana in 2022 reported a prevalence of 8.8%;8 Rwanda reported a prevalence of 2.0% over a 2 years period,9 and Ethiopia reported a prevalence of 11.51%.10 Furthermore, a prevalence of 4.3% was reported in northern Uganda11; in Kenya, prevalence of pre-eclampsia was estimated to be between 5.6% and 6.5%.12 In Tanzania, the prevalence of pre-eclampsia was reported to be 19.9% and 4.2% in different studies.4 13 As aforementioned, several studies have reported the prevalence of pre-eclampsia and associated risk factors across different countries in Africa; however, the results are inconclusive due to variations among populations and ethno-geographic groups.14 In fact, these studies were facility-based with small sample sizes and thus failed to provide in-depth data on the magnitude in the specific localities. Despite the rising prevalence of hypertensive disorders in Tanzania, little is documented about the prevalence of pre-eclampsia, its trends, risk factors and the knowledge among healthcare workers, pregnant women and the community across different regions and ethnic groups. This lack of information impedes the implementation of effective strategies and interventions to address this critical issue.

Recent studies have shown significantly elevated risks of pre-eclampsia following assisted reproductive technologies and in pregnancies characterised by reduced paternal antigen exposure, such as in nulliparous women or women who have different partners in different pregnancies.15 16 The risk is notably higher in twin pregnancies, where the disease often manifests more severely and at an earlier gestational age.17 Additionally, maternal age plays a critical role; women aged 35 years or older face approximately a twofold increased risk. Prepregnancy obesity is consistently linked to postpartum pre-eclampsia in a dose-dependent fashion, with a risk increase of up to 7.7-fold for those with body mass index (BMI) of greater than 40 kg/m².18 19 Furthermore, Black women have a 2–4 fold increased risk of developing postpartum pre-eclampsia compared with women of other races. Gestational diabetes stands out as an independent risk factor, particularly associated with late-onset cases.20 21 Maternal sleep disturbances, including sleep-disordered breathing and obstructive sleep apnoea, further contribute to this increased risk, as do systemic autoimmune diseases like systemic lupus erythematosus and antiphospholipid syndrome (APS).22 23

Pre-eclampsia manifests differently depending on the gestational age at onset, which serves as a key indicator of the disease’s severity. Babies born to mothers with early onset pre-eclampsia experience significantly higher rates of adverse outcomes compared with those with late onset. These include increased perinatal mortality, higher rates of stillbirths, low birth weight, fetal growth restriction and lower APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scores at the fifth minute.24–26 In terms of maternal outcomes, early onset pre-eclampsia is often associated with the need for early termination of pregnancy due to uncontrolled blood pressure, abnormal lab findings and severe clinical symptoms. Mothers in this group more frequently exhibit elevated liver enzyme levels, haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, higher diastolic blood pressure and longer hospital stays.27 In early onset cases, mothers tend to be at the extremes of reproductive ages (≤18 or ≥35 years) and face a greater risk of multi-organ involvement, including hepatic, haematologic, arterial and renal complications. In contrast, late onset pre-eclampsia is more frequently observed in women with higher pre-conception BMI.28 In low-resource settings like Tanzania, the burden of perinatal morbidity and mortality is compounded by the high rate of medically indicated preterm deliveries in these high-risk women in settings that lack both personnel and technological capacity to handle these delicate preterm babies. The frequent preterm births associated with pre-eclampsia result in babies with insufficient surfactant, making effective lung ventilation more challenging.26 Anticipated deliveries in such cases require the availability of appropriate resuscitation equipment and trained personnel resources that are often lacking in these settings.

All women with pre-eclampsia are at risk of rapid deterioration and severe complications, regardless of timing. These may include eclampsia, haemorrhagic stroke, HELLP syndrome, placental abruption, renal failure and pulmonary oedema.5 In fact, in recent years, pre-eclampsia is recognised as a systemic disease with widespread effects, which does not end with placental delivery, as commonly accepted for many years. Studies have shown that women who develop pre-eclampsia are more likely to carry protein-altering mutations in genes associated with cardiomyopathy.29 Women who survive pre-eclampsia have reduced life expectancy, with increased risks for long-term morbidities, including chronic hypertension, atherosclerotic morbidity, diabetes, stroke, cardiovascular and renal disease, besides pre-eclampsia in future pregnancies, while babies from a pre-eclamptic pregnancy have increased risks of neurodevelopmental disability, cardiovascular and metabolic diseases later in life.30–32

Pathophysiology of pre-eclampsia

Our understanding of the disorder is limited and influenced by misconceptions, and it has often been labelled as the ‘disease of theories’ due to the numerous schools of thought that drive research into this complex disease.33 The root word of pre-eclampsia is ‘eclampsia’, a term derived from the Greek word for ‘lightning’, reflecting how suddenly and unexpectedly convulsions may arise; this condition, recognised over 2000 years ago as a pregnancy-specific disorder, resolves with delivery. In the late 19th century, the similarity of the oedematous women with eclampsia to subjects with Bright’s disease and acute glomerulonephritis prompted urine testing for protein.34 35 This protein was indeed present in eclamptic women. Around the same time, the invention of the sphygmomanometer enabled non-invasive blood pressure measurement, revealing elevated levels in these women. Subsequent studies demonstrated that high blood pressure and proteinuria preceded seizures, leading to the modern understanding of pre-eclampsia as a condition characterised by new onset of hypertension and proteinuria before seizures occur.36

The most widely accepted and plausible explanation for the development of pre-eclampsia is the two-stage theory. This model describes the disease in two distinct but interconnected stages. The first stage involves impaired placentation and reduced placental perfusion, while the second stage is characterised by widespread maternal endothelial damage and dysfunction. This theory is particularly effective in explaining the pathophysiology of early-onset pre-eclampsia. In the first stage, the core issue arises from abnormal placental development, primarily due to inadequate trophoblast invasion into the spiral arteries.3 28 37 38 These spiral arteries are non-branching end arteries derived from the uterine arteries, extending into the endometrium and the inner myometrium. During a healthy pregnancy, these arteries undergo significant remodelling to meet the increasing demands of uteroplacental blood flow. They are physiologically transformed from high-resistance arterioles into dilated, low-resistance vessels with thin walls to ensure adequate perfusion.24 39 Pijnenborg et al40 outlined five stages of spiral artery remodelling. Stage 1 involves swelling of individual smooth muscle cells in the uterine spiral artery and endothelial vacuolation. In stage 2, interstitial trophoblasts begin to invade the perivascular tissues, disrupting the vascular smooth muscle layer. Stage 3 sees the appearance of endovascular trophoblasts, followed by their integration into the vessel wall as intramural trophoblasts in stage 4. Finally, stage 5 involves re-endothelialisation with newly formed endothelium and thickening of the subintima, which contains myofibroblasts. Several regulatory factors influence this remodelling process. Through this complex process, the spiral arteries become structurally suited to provide low vascular resistance and enhanced vasodilation, both of which are crucial for sufficient uteroplacental circulation and a successful pregnancy.28 In contrast, women who develop pre-eclampsia experience impaired spiral artery remodelling. This failure compromises placental development early in pregnancy, leading to reduced placental perfusion—the hallmark of the first stage of the disease.

The second stage involves maternal endothelial dysfunction, primarily driven by the overproduction of anti-angiogenic factors. Among these, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) are notably elevated in women with pre-eclampsia. These factors negatively impact both the function and structural integrity of the maternal endothelium. sFlt-1, a soluble form of the vascular endothelial growth factor (VEGF) receptor 1 (VEGF-1), has gained particular attention and is now used as a clinical marker for pre-eclampsia. It inhibits the proangiogenic effects of VEGF, which normally protect the endothelium and stimulate the production of nitric oxide and prostacyclin.24 28 38 Excess sFlt-1 disrupts these protective functions. Additionally, sEng may intensify the anti-angiogenic effects by further reducing nitric oxide production in endothelial cells and increasing vascular permeability. Together, these mechanisms lead to the endothelial dysfunction and systemic manifestations that define the clinical presentation of pre-eclampsia as illustrated in figure 1.

Emerging researchers have identified at least two subtypes of pre-eclampsia, namely early and late onset. Early onset pre-eclampsia (develops before 34 weeks of gestation) is predominantly attributed to placental causes, while late onset pre-eclampsia (develops at or after 34 weeks of gestation) appears to result from interactions between placental senescence and maternal genetic predisposition to cardiovascular and metabolic diseases. A hallmark of early-onset pre-eclampsia is oxidative stress of the syncytiotrophoblast, the cell type forming the epithelial layer of the placental villi in contact with maternal blood. Under oxidative stress, the syncytiotrophoblast releases a complex mix of factors, including pro-inflammatory cytokines, exosomes, anti-angiogenic agents and cell-free fetal DNA (cfDNA), into the maternal circulation. These factors disrupt maternal endothelial function, inducing a systemic inflammatory response that manifests clinically as pre-eclampsia.30 41 42 Conversely, late-onset pre-eclampsia is more likely attributed to an imbalance between normal maternal perfusion and the increasing metabolic demands of the placenta and fetus, coupled with a maternal predisposition to inflammation, a high BMI and/or hypertension.43 Moreover, following Medawar’s seminal essay on the fetus as ‘nature’s transplant’, the role of the maternal immune system in regulating successful pregnancy has been extensively studied. Key to this understanding is the immune system’s characteristics of memory and specificity, reflected in the increased incidence of pre-eclampsia in primigravidae (memory) and after a change of father (specificity).44

Recent studies have shown that certain gene variants play important roles in the development of pre-eclampsia. One of these genes is Fms-like tyrosine kinase 1 (FLT1) which encodes the VEGFR-1 which is notably upregulated in pre-eclamptic placentas leading to an overproduction of sFlt-1 that blocks other important factors like VEGF and PlGF (placental growth factors) from working properly, resulting in endothelial dysfunction and impaired placental angiogenesis.45 46 Subsequently, Angiopoietin-2 (ANGPT2), an angiopoietin that destabilises blood vessels in the absence of its counterpart Angiopoietin-1 (ANGPT1), is found elevated in pre-eclampsia, which disrupts the balance between pro-angiogenic and anti-angiogenic factors, leading to impaired angiogenesis and endothelial dysfunction, further exacerbating vascular leakage and inflammation.47 This pro-inflammatory environment activates the Nuclear Factor Kappa B (NF- κB) signalling pathway, a key transcription factor complex that regulates the expression of inflammatory cytokines and adhesion molecules, causing systemic inflammation, impaired placental development and endothelial dysfunction.48 Moreover, variants in genes regulating mitogen-activated protein kinase (MAPK) signalling cascade contribute to abnormal trophoblast differentiation and invasion, impairing placental development.49 Altogether, these gene changes lead to poor placental development, inflammation and high blood pressure, the signs of pre-eclampsia.

Prediction, prevention and management of pre-eclampsia

The early identification and screening of pregnant women at high risk for pre-eclampsia are paramount for reducing the significant morbidity and mortality associated with this condition. The application of angiogenic and antiangiogenic biomarkers in clinical practice can play a crucial role in this regard. Pre-eclampsia is characterised by alterations in angiogenic and antiangiogenic factors, such as sFlt-1, sEng, as well as PlGF, which are linked to adverse pregnancy outcomes. Quantification of the sFlt-1/PlGF ratio has proven to be a useful biomarker test for aiding diagnosing and predicting pre-eclampsia in the short term.50

Beyond these markers, first trimester levels of pregnancy-associated plasma protein A can predict pre-eclampsia and superimposed pre-eclampsia in the third trimester.51 Plasma cfDNA and human suppression of tumourigenesis have also been identified as diagnostic biomarkers for gestational hypertension and pre-eclampsia.52 53 Pentraxin 3, an acute-phase protein produced in response to inflammation, has emerged as a novel biomarker for predicting placental failure and is also linked to pre-eclampsia.54 Furthermore, Wakabayashi et al used peptidomic analysis to discover seven peptides (P-2081, P-2091, P-2127, P-2209, P-2378, P-2858 and P-3156) linked to HDP, suggesting their potential as diagnostic biomarkers. Interestingly, these peptides may also serve as indicators of cardiovascular risk in the general population.53 55 Current research is exploring the use of proteomic studies using mass spectrometry and protein microarray, urinary proteomics and metabolomics for the early detection and prognostication of pre-eclampsia.56–58 Predictive models incorporating specific metabolites such as arginine, glycerol, 3-hydroxyisovalerate, 2-hydroxybutyrate, acetone and citrate, either alone or in combination with uterine artery Doppler pulsatility index and maternal characteristics, have demonstrated potential for effective screening for early onset pre-eclampsia.59 Additionally, integrative bioinformatics and machine learning studies have identified five potential genetic biomarkers—CGB5, LEP, LRRC1, PAPPA2 and SLC20A1—that may aid in early detection of pre-eclampsia.60 A summary of the most clinically relevant biomarkers implicated in the development and progression of pre-eclampsia is presented in table 1.

To mitigate the risk of pre-eclampsia, healthcare professionals often recommend that high-risk women, such as those with prior history of pre-eclampsia, chronic hypertension, pregestational diabetes mellitus, obesity and twins pregnancy, APS and receipt of assisted reproduction should start low-dose aspirin (75 mg) during the late first trimester.61 Additionally, pregnant women in settings where dietary calcium intake is low, calcium supplementation at doses of 1500–2000 mg/day is recommended for the prevention of pre-eclampsia.62 63 These calcium supplements can reduce the risk of pre-eclampsia by more than a half and lower the likelihood of preterm births by about a quarter. Adopting these measures, alongside regular prenatal check-ups, is crucial for effectively preventing and managing pre-eclampsia and its associated complications. Despite the recommendation prescribed, implementing these preventive measures has been particularly difficult in LMICs. The high cost of calcium supplements, coupled with the complex dosing schedule requiring them to take calcium supplements three times per day and separate from iron-folic supplements, often hinders their inclusion as part of standard prenatal care. Furthermore, many women in LMICs face difficulties in accessing healthcare services and attending clinics regularly, making it difficult to consistently follow these recommendations and fully benefit from the interventions. A study conducted between Tanzania and India aiming at addressing these implementation barriers by exploring whether a low dose of calcium supplementation (500 mg/day) could be just as effective as the recommended high dose by WHO (1500 mg/day) in preventing pre-eclampsia. The results showed that low-dose calcium supplementation given as a single dose was as effective as high-dose calcium and could be a more practical and affordable option for resource-limited settings. If this is scaled up, it will make it easier for LMICs to adopt and implement as an intervening strategy.64 65

Alongside the administration of calcium supplements, regular prenatal check-ups and prophylactic use of low dose aspirin (75 mg) to high risk pregnant mothers: WHO recommends the use of magnesium sulphate (MgSO₄) for the prevention of eclampsia in women with severe pre-eclampsia and for the treatment of women with eclampsia, induction of labour for women with severe pre-eclampsia at a gestational age when the fetus is not viable or is unlikely to achieve viability within 1 or 2 weeks, early delivery for women with severe pre-eclampsia at term, use of antihypertensive medications for the control of blood pressure, and administration of pre-referral loading dose of MgSO₄ before the patient is transferred to a higher facility for the prevention and management of pre-eclampsia and eclampsia.66–68 Cautionally, Confidence and Grooves reported that the success of the care given depends on health workers’ adherence to the prescribed guidelines.69 Furthermore, research has shown that certain supplements and medications, including vitamin D, diuretics and the combination of vitamin C and vitamin E, are not recommended for preventing pre-eclampsia and its complications during pregnancy.63 Instead, expectant mothers are encouraged to follow evidence-based practices and seek guidance from healthcare professionals to ensure their health and the well-being of their baby. However, despite significant advancements in the prediction and prevention of preterm pre-eclampsia through combined screening and interventions, the prediction of term and postpartum pre-eclampsia remains limited, and there are currently no established preventive treatments available.

Knowledge, attitudes and practices on pre-eclampsia among healthcare workers, pregnant women and community

Early diagnosis with timely and effective management can help to reduce the dangers of pre-eclampsia and its associated complications. Avoiding delays that are currently occurring in diagnosis and management is critical in this regard. Based on the Three Delays Model, phases of delay have been identified; ‘phase 1 delays’ relate to delay in recognition of danger signs and decision to seek care, ‘phase 2 delays’ involve delay in reaching an appropriate source of care and ‘phase 3 delays’ encompass delay in obtaining adequate and appropriate treatment.70 In the context of pre-eclampsia, ‘phase 1 delays’ arise due to lack of knowledge and poor understanding among pregnant mothers on complications and risk factors and when to seek medical help.71 Recent studies have consistently identified a substantial knowledge gap among women, pregnant mothers and their partners regarding risk factors, signs, symptoms, prevention and management of pre-eclampsia.72 Additionally, a much larger proportion of community members held misconceptions, negative beliefs and attitudes toward this obstetrical complication.73

On the other hand, ‘phase 3 delays’ arise due to inadequate knowledge and skills in pre-eclampsia care among healthcare workers, apart from poor facilities and lack of medical supplies. A woman who comes to the antenatal care (ANC) or labour ward early to receive appropriate care while the nurse or midwife receiving the woman is not skilled in diagnosing and managing pre-eclampsia and its complications, both the woman and her unborn baby may face severe morbidity and/or deaths. Lack of core knowledge leads to poor decision making and management and contributes to delays in treatment and referrals.74 Studies had shown that the majority of the healthcare providers working from primary/lower healthcare facilities had inadequate knowledge and skills in care, prevention and management of pre-eclampsia.75–77 And since the primary healthcare facilities are the entry point for most patients in Tanzania, including pregnant women, this may impair service delivery and lead to delays in receiving the appropriate management which may contribute to poor maternal and newborn outcomes.78

Conclusions

Pre-eclampsia remains a major contributor to maternal and perinatal morbidity and mortality, underscoring the urgent need for early prediction, prevention and comprehensive management. Evidence from the literature emphasises that timely diagnosis, close monitoring and appropriate delivery are essential in reducing adverse outcomes. Strengthening health system capacity and advancing research into the underlying mechanisms and novel screening tools for early detection are critical to reducing the global burden of this condition and achieving maternal and newborn health targets.

Recommendations

Strengthening the response to pre-eclampsia requires investing in the training of front-line healthcare workers, particularly nurses and midwives, to ensure competency in emergency obstetric care, early recognition of complications, timely referral and effective management. ANC services should be reinforced by deploying sufficient skilled staff, providing mentorship for less experienced providers and promoting staff rotation between lower and higher-level facilities to enhance knowledge transfer. Early risk identification can be improved through first trimester Doppler assessment of uterine artery blood flow, incorporating diagnostic biomarkers and promotion of lifestyle measures such as maintaining healthy weight, balanced nutrition and regular exercise. Initiating antihypertensive treatment in high-risk women can further reduce pregnancy-related complications. Raising community awareness through culturally tailored education and the involvement of trusted community figures, complemented by health talks at ANC clinics and mass media campaigns, remains essential for improving care-seeking behaviour. Successful implementation of these measures depends on robust infrastructure, accessible clinical guidelines, adequate diagnostic tools and reliable supplies of essential medicines. Looking forward, integrating emerging innovations such as AI-driven predictive models and molecular classification into early screening protocols may enhance individualised care and strengthen preventive efforts.