THE INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort

Abstract

Background

Hypertension during pregnancy, including preeclampsia (PE) and its severe complication, eclampsia, remains a primary cause of maternal mortality globally. Eclampsia is a critical complication of PE that severely impacts maternal and neonatal health. Evidence regarding outcomes in pregnancies complicated by eclampsia, especially in developing nations, is limited.

Objective

This study aimed to compare the maternal and perinatal outcomes in patients with preeclampsia, both with and without eclampsia.

Study Design

This was a national, multicenter, observational, retrospective cohort study conducted in Indonesia. Data were gathered from medical records of patients who delivered at 30 hospitals across five principal islands in Indonesia between January 2022 and December 2023. The study included 1,808 cases with complete data who met the inclusion criteria, consisting of all pregnancies impacted by PE that culminated in delivery at the research sites. The sample was classified into 2 groups: the eclampsia group (n=151) and the non-eclampsia group (n=1657). Primary outcomes examined included maternal outcomes (eg, severe morbidity, maternal mortality), intrapartum management, labor complications, and perinatal outcomes (eg, preterm birth, neonatal morbidity, neonatal death). Statistical analysis utilized SPSS version 29, employing independent t-tests or Mann-Whitney U tests for continuous data, and Chi-square or Fisher's exact tests for categorical variables, with results expressed as numerical percentages, mean ± SD, or median (minimum-maximum).

Results

The overall incidence of PE during the study period was 5.3% (6763 out of 127,604 births). Among PE patients with complete data (n=1808), the incidence of eclampsia was 8.35% (151 cases). Pregnant women with eclampsia were significantly younger, more frequently nulliparous, and had elevated diastolic blood pressure compared to the noneclamptic cohort (p<.05). Eclampsia was associated with markedly greater maternal morbidity, including HELLP syndrome (27.8% vs 10.7%; RR: 2.85), hypertensive emergencies (35.1% vs 21.4%; RR: 1.80), CVA (2.0% vs 0.1%; RR: 18.01), and ICU admission (34.4% vs 13.2%; RR: 2.86) (p<.05). The eclampsia cohort also had a higher likelihood of cesarean section delivery (95.4% vs 83.7%) and a markedly elevated incidence of seizures during labor (31.3% vs 0.0%). Perinatal morbidity was also greater in the eclampsia cohort, with increased preterm birth rates (52.3% vs 42.5%; RR: 1.35), lower absolute and percentile birth weight, lower Apgar scores at 1 minute (<7: 76.2% vs 46.3%; RR: 1.80) and 5 minutes (<7: 38.4% vs 21.5%; RR: 1.96), increased NICU admissions (32.2% vs 22.8%; RR: 1.59), and a greater prevalence of respiratory distress syndrome (RDS) (32.2% vs 12.9%; RR: 2.80), necrotizing enterocolitis (NEC) (4.7% vs 0.8%; RR: 7.00), and neonatal sepsis (12.1% vs 3.8%; RR 3.60) (p<.05).

Conclusions

In this Indonesian multicenter cohort, preeclamptic pregnancies complicated by eclampsia were associated with significantly higher severe maternal and perinatal morbidity compared to those without eclampsia. These findings underscore the critical importance of early detection and prompt management of preeclampsia, including the timely use of MgSO4 for seizure prophylaxis, strict blood pressure control, and timely delivery of patients with severe preeclampsia, to prevent progression to eclampsia and mitigate adverse outcomes.

AJOG Global Reports at a Glance.

Why was this study conducted?

This study aimed to assess the impact of eclampsia on maternal and perinatal outcomes in women with preeclampsia, utilizing data from a substantial national multicenter cohort in Indonesia.

Key findings

This study found that eclampsia occurred in 8.3% of preeclamptic pregnancies, significantly increasing the risks of HELLP syndrome, stroke, ICU admission, preterm birth, and neonatal complications such as RDS, NEC, and sepsis.

What does this add to what is known?

This research presents significant national evidence from Indonesia regarding the major effect of eclampsia on maternal and perinatal health. It emphasizes the necessity of early detection, magnesium sulfate prophylaxis, and prompt delivery to mitigate severe outcomes.

Introduction

Hypertension during pregnancy is the leading cause of maternal mortality globally (46,000 annually), accounting for 16%, after hemorrhage at 27% and indirect obstetric causes at 23%.¹ Preeclampsia and eclampsia account for approximately ten percent of maternal mortality in Asia and Africa, and 25% in Latin America.² The highest incidence of maternal mortality attributable to hypertension has been identified in Latin America and the Caribbean. Preeclampsia affects 2%−8% of all pregnancies, as per WHO data.² Preeclampsia results in 500,000 perinatal death each year.

Eclampsia is a severe consequence of preeclampsia, characterized by generalized tonic-clonic seizures, coma, and loss of consciousness. The World Health Organization estimates the global prevalence of eclampsia at 0.3%. The incidence significantly differs by region, with elevated rates of 0.5% observed in low-income and developing countries.³ The exact mechanism of eclampsia remains uncertain; nevertheless, various theories have been proposed, including disruption of the blood-brain barrier (BBB), autoregulation of cerebral blood flow, and the effects of toxic circulating products in preeclampsia.⁴

Eclampsia is a critical complication of preeclampsia that impacts maternal and neonatal health. Numerous research indicate that eclampsia worsens maternal and perinatal outcomes. Evidence regarding outcomes in pregnancies complicated by eclampsia, especially in underdeveloped nations, remains scarce. This is the first national, multicenter study in Indonesia that compares maternal and perinatal outcomes in patients with preeclampsia, both with and without eclampsia.

Methods

Study design, sampling methods, ethical approval, and randomization

This is a multicenter observational retrospective cohort study conducted in Indonesia. This study was organized and executed by the Himpunan Kedokteran Fetomaternal Indonesia (Indonesian Maternal Fetal Medicine Association). Data were gathered from 30 hospitals throughout 5 principal islands in Indonesia from January 2022 to December 2023. Data were acquired from medical records through both manual and electronic methods. The ethics council of Airlangga University Hospital has granted ethical approval for this research (approval no. 052/KEP/2024, protocol number UA-02-24074). The inclusion criteria comprised of all pregnancies impacted by PE culminating in delivery at the hospital where the research study was conducted between January 2022 and December 2023. Exclusion criteria were implemented just when pregnancy outcome data were inadequately recorded in medical records. The sample size denotes the cumulative sampling performed during the study period, modified according to the inclusion and exclusion criteria. The total number of pregnant women with preeclampsia who delivered at the research sites was 6763; however, complete data were obtained for only 1,808 cases. The sample was subsequently classified into two groups based on the occurrence of eclampsia, that is, the eclampsia group versus the non-eclampsia group. Eclampsia is identified by the manifestation of generalized tonic-clonic seizures in a woman with preeclampsia. The emergency management of preeclampsia and eclampsia adheres to the national guidelines for preeclampsia management (2016) issued by the Indonesian Ministry of Health, as well as the peripartum hypertension management guidelines published by the Indonesian Society of Hypertension (2025).

Primary outcomes and definition

This study examined maternal outcomes, intrapartum management, labor complications, laboratory data, and perinatal outcomes, comparing eclamptic cases with non-eclamptic patients with preeclampsia. Maternal outcomes encompassed the type of preeclampsia, preterm birth, severe morbidity (including pulmonary edema, HELLP syndrome, acute kidney injury, hypertensive emergency, cerebrovascular accident, and intensive care unit admission), and maternal mortality. HELLP syndrome was diagnosed based on the following criteria: hemolysis, increased liver enzymes (AST or ALT above twice the upper limit of normal), and a blood platelet count below 100,000 µL.^5,6 Acute kidney injury (AKI) is identified by elevated BUN levels, serum creatinine exceeding the normal threshold or over 50% of baseline, or the occurrence of oliguria (urine output <0.5 mL/kg BW/hour).⁷ A hypertensive emergency in pregnancy is characterized by a severe-range blood pressure, defined as a systolic blood pressure (SBP) of >160 mm Hg or a diastolic blood pressure (DBP) of ≥110 mm Hg, which persists for at least 15 minutes and is associated with indications of acute end-organ damage.⁸ Delivery complications encompassed seizures, cerebrovascular accident (CVA), postpartum hemorrhage (HPP), and uterine atony. Perinatal outcomes encompassed gestational age at birth, infant weight (both absolute and percentile), intrauterine growth restriction (IUGR), intrauterine fetal demise (IUFD), Apgar scores at 1 and 5 minutes, duration of NICU admission, neonatal morbidity (including sepsis, RDS, NEC, and intraventricular hemorrhage (ICH)), and neonatal death.

Data analysis and statistics

Data analysis and statistical evaluation were conducted using SPSS version 29. Categorical data will be expressed as numerical percentages. Numerical data will be displayed in accordance with its distribution. If the data conform to a normal distribution, they will be shown as mean±SD; conversely, if the numerical data deviate from a normal distribution, they will be represented as median (minimum-maximum). All variables were analyzed for differences between the eclamptic group and the non-eclamptic group. Independent t-tests or Mann-Whitney U tests will be utilized for continuous data, whereas Chi-square or Fisher's exact tests will be applied for categorical variables, as deemed appropriate.

Results

The incidence of PE during the study periods was 6763 out of 127,604 births, representing 5.3%. Among the 6763 PE patients, 1808 (26.73%) with complete data were included in this study following a verification of data completeness. Participants were categorized into 2 groups: 151 (8.35%) with eclampsia and 1657 (91.65%) without eclampsia. The overall incidence of eclampsia among all cases of preeclampsia was around 2.23% (151 cases/6763 PE cases), whereas the prevalence among all deliveries was 0.12% (151 cases/127,604 live birth) among our entire population. Table 1 illustrates the differences in overall maternal characteristics between the 2 cohorts. Pregnant women with eclampsia were younger, more frequently nulliparous, and had elevated diastolic blood pressure compared to the non-eclamptic cohort (p<.05). Nulliparity in women with preeclampsia elevated the risk of eclampsia by 1.6-fold (95% CI: 1.39−2.05). According to prior health records, the eclamptic cohort exhibited a lower rate of prior miscarriage and diabetes mellitus compared to the noneclamptic cohort (p<.05).

Table 1.

General maternal characteristics

General characteristic	Noneclampsia (n=1657) n (%)	Eclampsia (n=151) n (%)	P value	RR (95% CI)
Maternal ages	32.08±7.1	28.04±7.15	<.001	0.60 (0.44–0.82)
≥35 yo	622 (37.6%)	31 (20.5%)	<.000a
20-35 yo	1000 (60.4%)	105 (59.5%)
<20 yo	34 (2.1%)	15 (9.9%)
BMI on admission	28.74±6.32	28.61±5.85	1.000c	-
Systolic BP	165.32±20.68	168.13±24.63	.111c	-
Diastolic BP	101.22±14.75	105.25±17.23	<.001c	-
Obesity	564 (34.5%)	56 (39.7%)	.208b	-
Obesity class
Class 1	326 (57.8%)	37 (66.1%)	.403	-
Class 2	156 (27.7%)	11 (19.6%)
Class 3	82 (14.5%)	8 (14.3%)
Parity			<.001b	1.69 (1.39–2.05)
Nulliparity	462 (27.9%)	65 (43.0%)
Multiparity	1193 (72.1%)	86 (57.0%)
IVF pregnancy	1 (0.1%)	0 (0%)	1.000a	-
Multiple pregnancy	61 (3.8%)	5 (3.4%)	1.000b	-
History of disease
History of miscarriage	402 (24.3%)	22 (14.6%)	.035b	0.66 (0.44–0.97)
History of IUGR	219 (13.2%)	22 (14.6%)	.440b	1.21 (0.81–1.80)
Chronic hypertension	295 (17.8%)	29 (19.2%)	.409b	1.18 (0.84–1.66)
DM	79 (4.8%)	1 (0.7%)	.018b	0.15 (0.02–1.08)
Renal disease	13 (0.8%)	4 (2.6%)	.036a	3.69 (1.22–11.18)
Autoimunne disease	22 (1.3%)	3 (2.0%)	.434a	1.64 (0.50–5.40)
History of PE	203 (12.3%)	19 (12.6%)	.700b	1.12 (0.73–1.74)

^aFisher exact test

^bChi-square

^cMann-Whitney.

Akbar. The INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort. AJOG Glob Rep 2025.

The eclampsia cohort exhibited markedly greater maternal morbidity compared to the non-eclampsia cohort, encompassing HELLP syndrome, hypertensive emergencies, CVA and ICU admission (p<.05). Eclampsia elevated the risk of CVA by 18 times (95% CI: 3.03−106.89; p=.004). Regarding intrapartum care, the eclampsia cohort exhibited a higher likelihood of cesarean section delivery (95% vs 83.7%) compared to the non-eclampsia cohort. Approximately 46 women (30.5%) in the eclampsia group experienced seizures during labor. No cases of postpartum eclampsia were observed in this series. Table 2 presents a review of maternal outcomes, intrapartum management, and complications.

Table 2.

Maternal outcomes

Maternal outcomes	Noneclampsia (n=1657) n (%)	Eclampsia (n=151) n (%)	P value	RR (95% CI)
Severity PE			.239b	-
PE	158 (9.6%)	10 (6.7%)
Severe PE	1490 (90.4%)	140 (93.3%)
Onset PE			.288b	-
Early-onset PE	544(32.8%)	56 (37.1%)
Late-onset PE	1113 (67.2%)	95(62.9%)
Pulmonary edema	91 (5.5%)	13 (8.6%)	.115b	-
HELLP syndrome	177 (10.7%)	42 (27.8%)	<.001b	2.85 (2.14–3.80)
Acute kidney injury	50 (3.0%)	3 (2.0%)	.794a	-
Emergency hypertension (>180/110 mm Hg)	354 (21.4%)	53 (35.1%)	<.001b	1.80 (1.43–2.27)
CVA	2 (0.1%)	3 (2.0%)	.004a	18.01 (3.03–106.89)
Preterm birth < 37 wk	704 (42.5%)	79 (52.3%)	.001b	1.35 (1.15–1.57)
Preterm birth < 34 wk	510 (30.8%)	54 (35.8%)	.053b	1.27 (1.02–1.59)
ICU admission	218 (13.2%)	52 (34.4%)	<.001	2.86 (2.23–3.67)
Maternal death	20 (1.2%)	4 (2.6%)	.107a	-
Management
Aspirin during ANC	74 (4.5%)	5 (3.3%)	.804b	-
MgSO4	1409 (87.3%)	138 (92.6%)	<.001b	1.18 (1.15–1.21)
Steroid for fetal lung maturation	626 (39.5%)	54 (39.1%)	.824b	-
Mode of delivery			<.001b	0.32 (0.15–0.66)
Vaginal	266 (16.3%)	7 (4.6%)
CS	1363 (83.7%)	144 (95.4%)
Labour complications
Seizure on labor	0 (0.0%)	46 (31.3%)	<.001a	-
CVA on labor	1 (0.1%)	1 (0.7%)	.148a	-
Post partum hemmorrhage (PPH)	31 (1.9%)	4 (2.6%)	.339a	-
Uterine atony	28 (1.7%)	2 (1.3%)	1.000a	-

^aFisher exact test

^bChi-square.

Akbar. The INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort. AJOG Glob Rep 2025.

The eclampsia cohort exhibited greater perinatal morbidity compared to the non-eclampsia cohort. This was marked by increased preterm birth rate, reduced absolute and percentile birth weight, an increased occurrence of Apgar scores below 7 at 1 and 5 minutes, NICU admissions, and a greater prevalence of RDS, NEC, and newborn sepsis (p<0.05). Eclampsia elevated the risk of NEC by 7 times (95% CI: 2.8−17.5) and neonatal sepsis by 3.6 times (95% CI: 2.19−5.92). Table 3 presents a summary of perinatal outcomes. The summary of the significant maternal and perinatal outcomes is illustrated in figure 1.

Table 3.

Perinatal outcomes

Perinatal outcomes	Noneclampsia (n=1657) n (%)	Eclampsia (n=151) n (%)	P value	RR (95% CI)
GA on delivery	34.39±4.09	34.16±3.8	.459c	-
Birthweight (gram)	2261.28±874.95	2081.94±810.2	.012c	-
Birthweight percentile	41.66±33.55	34.72±30.92	.026c	-
	43.11±7.16	42.91±6.27	.447c	-
IUGR	279 (16.8%)	23 (15.2%)	1.000b	-
Intra uterine fetal death (IUFD)	90 (5.4%)	7 (4.6%)	1.000b	-
Apgar score 1st minutes			<.001b	1.80 (1.64–1.97)
≥7	890 (53.7%)	36 (23.8%)
<7	767 (46.3%)	115 (76.2%)
Apgar score 5th minutes			<.001b	1.96 (1.57–2.43)
≥7	1301 (78.5%)	93 (61.6%)
<7	356 (21.5%)	58 (38.4%)
NICU admission	363 (22.8%)	48 (32.2%)	<.001b	1.59 (1.24–2.03)
Respiratory distress syndrome (RDS)	206 (12.9%)	48 (32.2%)	<.001b	2.80 (2.15–3.64)
Intrcramial hemorrhage (ICH)	2 (0.1%)	1 (0.7%)	.213a	-
Necrotizing Enterocollitis (NEC)	12 (0.8%)	7 (4.7%)	<.001a	7.00 (2.80–17.50)
Neonatal sepsis	60 (3.8%)	18 (12.1%)	.001b	3.60 (2.19–5.92)
Neonatal death	110 (6.8%)	13 (8.7%)	.286b	-

^aFisher exact test

^bChi-square

^cMann-whitney.

Akbar. The INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort. AJOG Glob Rep 2025.

Figure 1.

Maternal outcomes (Panel A) and perinatal outcomes (Panel B) were significantly worse in the eclampsia group compared with preeclampsia alone

Percentages for each group are shown within bars, and risk ratios (RR) with 95% confidence intervals (CI) are displayed above each variable.

Akbar. THE INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort. AJOG Glob Rep 2025.

Discussion

Principal findings

In our multicenter Indonesian cohort, patients who developed eclampsia experienced dramatically higher rates of severe maternal and perinatal morbidity. The eclampsia cohort exhibited markedly greater maternal morbidity compared to the non-eclampsia cohort, encompassing HELLP syndrome, hypertensive emergencies, CVA and the need for ICU admission. This group also showed a higher rate of preterm birth, low birth weight, low Apgar scores, NICU admission, and severe neonatal morbidities (RDS, NEC, neonatal sepsis). The clear message for clinicians is that eclampsia confers substantial additional risk, and every effort should be made to identify and manage high-risk preeclampsia before seizures occur.

Results comparison

The results of this study align with prior research on pregnancy outcomes in eclampsia.⁹ A smaller study conducted in Ethiopia with 311 participants diagnosed with preeclampsia revealed that women with eclampsia exhibited a greater incidence of adverse maternal outcomes in comparison to those with severe and mild preeclampsia (63% vs 30.1% vs 6.8%). This was linked to a heightened risk of HELLP syndrome, aspiration pneumonia, and AKI.¹⁰ Eclampsia markedly elevates the probability of preterm birth. This aligns with a secondary study of the World Health Organization Multinational Survey on Maternal and Newborn Health (WHOMCS) database. This cross-sectional study encompassed 357 healthcare facilities spanning 29 nations in Africa, Asia, Latin America, and the Middle East. The prevalence of preterm delivery (<37 weeks) was greater in eclampsia than in preeclampsia and in women without preeclampsia (39.8% vs 30.1% vs 7.1%). The study additionally revealed a greater prevalence of low birth weight, lower Apgar scores at 5 minutes, and the occurrence of at least one major neonatal problem in the eclampsia cohort compared to the preeclampsia cohort and women with normal pregnancies. Maternal near-miss cases occurred 8 times more frequently in women with pre-eclampsia and escalated to as much as sixty times more frequently in women with eclampsia, in comparison to women without these conditions.¹¹ A separate study in India indicated that eclampsia heightened the risk of (partial) HELLP syndrome and IUFD in comparison to severe preeclampsia.¹²

Clinical implications

This research demonstrates that in Indonesia, eclampsia is strongly associated with a higher rate of severe maternal and perinatal morbidity and mortality. Eclampsia increases the risk of HELLP syndrome, hypertensive emergencies, CVA, ICU admission, cesarean section, and seizures during labor. Eclampsia has been demonstrated to contribute to severe perinatal morbidity, including prematurity, NICU admission, neonatal sepsis, NEC, RDS, diminished Apgar scores, lower birth weight, and perinatal mortality.

Our results reinforce existing guidelines that call for aggressive management of severe preeclampsia to avert eclampsia and its sequelae. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) emphasize early identification and prompt intervention for hypertensive disorders of pregnancy.^13,14 All these practices are incorporated into national standards for the management of preeclampsia and must be implemented in all hospitals across Indonesia. In practical terms, key clinical measures include:

• •Seizure Prophylaxis: Administer MgSO4 to women with severe preeclampsia, as this therapy is proven to prevent eclamptic seizures (WHO estimates it can reduce the risk of eclampsia by over 50%). In this study, 87.3% of patients in the non-eclampsia group received MgSO4, compared to 92.6% in the eclampsia group. In the cohort with severe preeclampsia, the proportion of individuals administered MgSO4 in the non-eclampsia group was 94.56%, compared to 98.57% in the eclampsia group. Ensuring MgSO4 is readily available and used appropriately – especially in resource-limited settings where its uptake has been suboptimal – is a vital step to reduce eclampsia incidence.¹⁴ With good antenatal care and proper management of preeclampsia in hospital the rate of eclampsia should be close to zero. The absence of postpartum eclampsia in all cases, as demonstrated in this study, can be explained to the routine administration of MgSO4 in cases of severe preeclampsia.
• •Blood Pressure Control: Treat severe hypertension (≥160/110 mm Hg) immediately with rapid-acting antihypertensives to prevent stroke and other end-organ damage.¹⁴ Our finding of a markedly elevated stroke risk in the eclampsia group highlights the need for diligent blood pressure management in preeclamptic patients.^15,16 Clinicians should follow protocols (eg, IV labetalol [not available in Indonesia], hydralazine or nifedipine) to promptly control critical blood pressures, as recommended by obstetric emergency guidelines, to avert intracerebral hemorrhage or hypertensive encephalopathy. Antihypertensive medicine is simultaneously treated with MgSO4 seizure prophylaxis to rapidly mitigate the risk of eclampsia. The primary antihypertensive medication recommended is oral nifedipine, which may be administered alongside oral methyldopa in instances of severe hypertension. MgSO4 is delivered intravenously according to the Zuspan regimen.
• •Optimal Timing of Delivery: Do not unduly prolong a high-risk pregnancy once severe preeclampsia is diagnosed. Timely delivery is the definitive intervention for preeclampsia and eclampsia. WHO guidance stresses that determining when to end the pregnancy is critical to preventing complications.¹⁴ Our data support this – expediting delivery in worsening preeclampsia can forestall the full-blown eclamptic syndrome and protect maternal organs. When preterm delivery is unavoidable, administer antenatal corticosteroids to accelerate fetal lung maturity, as this can reduce RDS severity in the newborn.^17,18 Avoid emergency CS in eclamptic patients without prior hemodynamic stabilization: Eclampsia is a maternal crisis. Only after maternal stabilization, fetal monitoring will again influence obstetrical management.
• •Neonatal Preparedness: Anticipate and plan for neonatal complications. Given the significantly higher likelihood of preterm birth and low birth weight in eclamptic pregnancies, neonatology teams should be on standby for prompt NICU admission and care. Administration of MgSO4 to the mother may also offer neuroprotection to preterm infants.¹⁹ Ensuring that facilities can provide advanced neonatal support (ventilation for RDS, antibiotics for possible sepsis, parenteral nutrition, etc.) is crucial to improve perinatal outcomes in these cases.

The severe complications observed in eclamptic patients can be explained by the pathophysiology of advanced preeclampsia. Eclamptic seizures and neurological damage are thought to result from loss of normal cerebral autoregulation at extreme blood pressures, leading to endothelial injury in the brain, breakdown of the blood–brain barrier, and vasogenic cerebral edema or hemorrhage.²⁰ This mechanism is analogous to hypertensive encephalopathy and underlies the greatly increased risk of stroke in eclampsia. Additionally, preeclampsia is fundamentally a syndrome of diffuse endothelial dysfunction triggered by a dysfunctional placenta that releases anti-angiogenic and inflammatory factors into the maternal circulation.²¹ Progression to eclampsia likely reflects a failure of the maternal system to compensate for this widespread endothelial injury.^22,23 For example, the higher incidence of HELLP syndrome in our eclampsia group is consistent with more severe maternal microvascular damage (hemolysis, liver ischemia and platelet consumption) in these patients. In essence, eclampsia represents the extreme end of the preeclampsia spectrum, wherein uncontrolled blood pressure and severe endothelial derangements precipitate multi-organ complications (hepatic rupture, acute kidney injury, disseminated intravascular coagulation) and life-threatening emergencies for the mother.^24,25 These findings reinforce the importance of aggressive prophylactic and therapeutic measures in severe preeclampsia to prevent patients from reaching this critical tipping point.

The excess perinatal morbidity in eclamptic pregnancies also has clear clinical explanations. Mothers with eclampsia often require urgent delivery irrespective of gestational age to save the mother’s life, resulting in a higher frequency of premature births. Consequently, neonates born to eclamptic mothers are at greater risk of complications of prematurity – such as RDS and NEC – and they more often require prolonged NICU care for issues like respiratory support and feeding assistance. Severe maternal hypertension and uteroplacental insufficiency can lead to fetal growth restriction and chronic fetal hypoxia, which may compromise the newborn’s transition and immune defences.26, 27, 28, 29 It is notable that in our study the eclampsia group’s infants had higher rates of neonatal sepsis; this likely reflects their preterm status and possible intrauterine inflammation or exposure to maternal infection (eg, placental abruption or chorioamnionitis can accompany severe preeclampsia). Prior studies have similarly found that infants born to pregnancies complicated by preeclampsia have higher rates of NICU admission, respiratory distress, and infection than those from normotensive pregnancies.^30,31 These observations underscore the importance of neonatal preparedness: when managing a woman with severe preeclampsia or eclampsia, clinicians should involve neonatologists early and ensure that facilities for advanced neonatal support are available. Administration of antenatal steroids (as mentioned) and MgSO4 (for fetal neuroprotection) are evidence-based interventions to improve neonatal outcomes, and prompt neonatal intensive care can address complications like RDS (with surfactant therapy) or sepsis.^17,19,32 The integrated pathophysiologic cascade and clinical implications of eclampsia is illustrated in Figure 2.

Figure 2.

Integrated clinical pathway of eclampsia, linking maternal endothelial injury and cerebral dysfunction to severe maternal and perinatal complications, with key preventive and therapeutic interventions

Akbar. THE INAPRES (Indonesia Preeclampsia Study): impact of eclampsia on maternal and perinatal outcomes among women with preeclampsia: findings from a National Multicenter Cohort. AJOG Glob Rep 2025.

A national guideline for the management of preeclampsia, established in 2016, is obligatory for all hospitals and healthcare facilities in Indonesia. The key problem lies in the implementation of this guideline across all healthcare facilities in Indonesia, particularly in lower-tier hospitals and primary healthcare centers. Moreover, Indonesia's geographical configuration, comprising tens of thousands of islands, presents a considerable barrier for the equitable allocation of healthcare resources, including the execution of this guideline. Various initiatives have been implemented, encompassing training at primary and secondary hospitals for the screening, early diagnosis, and emergency management of preeclampsia, specifically eclampsia. Additionally, we regularly do in-hospital simulations on the management of preeclampsia-eclampsia in accordance with relevant standards.

Research implications

Our findings underscore that eclampsia, though relatively infrequent, dramatically worsens maternal outcomes in preeclamptic pregnancies (eg, an ∼18-fold higher risk of stroke). This stark impact highlights several critical gaps and unanswered clinical questions. First, better tools are needed to identify which women with preeclampsia are at highest risk for seizures. Traditional clinical monitoring has limitations – notably, up to 25% of eclamptic seizures occur without antecedent severe hypertension, making risk stratification difficult.³³ Developing predictive models and biomarkers for early warning is a research priority. For example, placental growth factor (PlGF) testing has shown promise in predicting severe complications of preeclampsia (including eclampsia) and speeding up diagnosis.^34,35 However, randomized trials are still required to determine whether incorporating such biomarker-based tools into clinical decision-making (for hospital admission, intensified monitoring, or early intervention) can actually reduce the incidence of eclampsia.³³ Prospective studies to refine clinical risk scoring (potentially combining symptoms, blood pressure trends, and laboratory markers) could enable more timely prophylactic treatment for those in danger of deteriorating to eclampsia.

Another crucial area for future research is the optimization of preventive and therapeutic protocols for eclampsia. MgSO4 remains the cornerstone for seizure prophylaxis in preeclampsia, but the ideal regimen and duration of therapy have not been conclusively defined. Questions remain about how best to balance efficacy with safety: for instance, what is the minimum effective duration of postpartum magnesium prophylaxis? Emerging evidence suggests that shorter magnesium infusions (eg, 12 hours instead of the traditional 24 hours) do not significantly increase the risk of eclamptic seizures, but existing studies are underpowered and unable to render firm conclusions.³⁶ Adequately powered clinical trials are needed to confirm the shortest safe duration of magnesium therapy and to establish evidence-based guidelines for its use after delivery. Similarly, it is unknown whether women who develop severe preeclampsia for the first time in the late postpartum period (more than 48 hours after delivery) would benefit from MgSO4prophylaxis at that time – a scenario not well addressed in current guidelines and one that warrants investigation.³³ Future comparative studies might also explore adjunctive anticonvulsant strategies for cases where MgSO4 appears insufficient, although magnesium’s superiority over other agents (eg, phenytoin or benzodiazepines) has been well documented in past trials.³⁶ Beyond seizure prophylaxis, there is a need for research into optimal blood pressure management protocols specifically to reduce eclampsia risk. Early aggressive treatment of severe hypertension has been associated with reduced eclampsia rates, yet the implementation of such protocols on a broad scale and their direct impact on preventing seizures remain areas for quality improvement research.

Strength and limitation

A key strength of this study is its novel focus on directly comparing pregnancy outcomes between preeclampsia with and without eclampsia, an analysis rarely reported in the literature. Most prior studies have examined women with preeclampsia or eclampsia in comparison to normotensive pregnancies, rather than isolating the incremental impact of an eclamptic episode in a preeclamptic population. By addressing this gap, our study provides specific insights into how the development of eclampsia exacerbates maternal and perinatal outcomes. In addition, the scale and scope of our investigation are noteworthy. To our knowledge, it is the first and largest multicenter study of preeclampsia in Indonesia, encompassing 30 hospitals across five major islands. This broad geographic coverage and large sample size offer an extensive overview of varied clinical settings and enhance the generalizability of our findings within the country. Furthermore, the inclusion of comprehensive outcome measures (maternal complications, intrapartum management, laboratory parameters, and neonatal outcomes) strengthens the analysis by capturing a wide spectrum of clinically relevant endpoints.

Despite these strengths, certain limitations should be acknowledged. The retrospective cohort design, which relied on extraction of data from medical records, inherently carries risks of information bias and unmeasured confounding. We had limited control over data quality and completeness, and causality cannot be established from observational associations. Notably, incomplete and missing data were a significant issue: of 6,763 identified preeclampsia cases during the study period, only 1,808 (26.7%) had sufficiently complete records to be included in the analysis. This attrition raises concern for potential selection bias if the excluded cases – possibly those from more resource-limited centers or with poorer documentation – differed in important ways from included patients. Unfortunately, data on near-misses were not collected.

Additionally, as a hospital-based study conducted at mainly tertiary referral centers, the cohort may overrepresent more severe cases and may not fully capture outcomes in lower-level facilities or the general community. These factors could limit the external validity of the results. Finally, variations in clinical management across the multiple centers were not controlled for, which could introduce heterogeneity in outcomes. In summary, while our study offers robust national data on preeclampsia and eclampsia outcomes, its findings should be interpreted in light of the above limitations. Proper caution is warranted in generalizing the results, and prospective studies would be valuable to confirm our observations.

Conclusion

In this multicenter retrospective cohort study in Indonesia, preeclamptic pregnancies complicated by eclampsia were associated with significantly higher maternal and perinatal morbidity than those without eclampsia. These findings underscore the critical importance of early detection of preeclampsia and prompt management to prevent progression to eclampsia, including the use of MgSO4 for seizure prophylaxis, strict blood pressure control, and timely delivery to mitigate adverse outcomes. Strengthening these interventions in clinical practice is essential to improve maternal and neonatal outcomes, and further clinical research is warranted to refine preventive strategies and ultimately reduce the burden of eclampsia.

Consent to participate

The Ethics Committee of Airlangga University Hospital has waived the requirement for informed permission to participate, owing to the retrospective study design (all data were sourced from medical records).

Declaration of generative AI in scientific writing

During the preparation of this work the author(s) used CHATGPT in order to To propose ideas related to writing and create clustered bar figure. We also used QUILLBOT to check the grammar and paraprhasing sentences. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the published article.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request

CRediT authorship contribution statement

Muhammad Ilham Aldika Akbar: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Ernawati: Writing – review & editing, Visualization, Validation, Supervision. Manggala Pasca Wardhana: Writing – review & editing, Visualization, Validation, Supervision, Resources, Formal analysis. Ruth Widhiati Raharjo Putri: Writing – review & editing, Validation, Supervision, Methodology, Investigation, Formal analysis. Anak Agung Gede Putra Wiradnyana: Writing – review & editing, Validation, Supervision, Methodology, Investigation. Dhanny Primantara Johari Santoso: Writing – review & editing, Validation, Supervision, Methodology, Investigation. Wiku Andonotopo: Writing – review & editing, Visualization, Validation, Supervision, Methodology, Investigation. Gustaaf Dekker: Writing – review & editing, Visualization, Validation, Supervision, Formal analysis, Conceptualization. Rozi Aditya Aryananda: Writing – review & editing, Validation, Supervision, Software, Methodology, Formal analysis.