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Open research questions in Pregnancy and preeclampsia studies

92 unresolved questions extracted from the limitations and future-work sections of 848 Pregnancy and preeclampsia studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • It also compares the traditional PE prediction approaches with the ML-based PE prediction approaches, highlights the state of the art in PE prediction, and suggests open issues for future research.

    Models, Applications, and Open Issues in the Intelligent Prediction of Preeclampsia: A Review · 2026 · DOI

  • Future research in the field of preeclampsia will likely focus on improving early prediction of the disease and developing targeted therapeutic approaches. New technologies, including genomic analyses, proteomics, and predictive models based on contemporary scientific knowledge, may significantly improve the identification of women at high risk of developing preeclampsia already in early pregnancy. Another promising area of research involves the development of novel pharmacological therapies aimed at correcting angiogenic imbalance and improving placental function. Although these measures alone cannot completely prevent the disease, they contribute to improved maternal cardiovascular health and more favorable pregnancy outcomes. Although delivery is currently the only definitive treatment, future therapeutic strategies may enable prolongation of pregnancy and improvement of neonatal outcomes.

    Preeclampsia: A Review of Contemporary Concepts · 2026 · DOI

  • Based on the findings of this study, it is recom‐ mended that mothers with SCH receive enhanced monitoring and specialized care to prevent known complications of this condition and avoid adverse pregnancy outcomes. This targeted approach should 62 focus particularly on the early detection and man‐ agement of preterm labor risks and potential miscar‐ riage, while maintaining standard obstetric care for other pregnancy parameters that showed no signif‐ icant association with SCH. The implementation of such specialized monitoring protocols could signifi‐ cantly improve maternal and neonatal outcomes in SCH‐affected pregnancies.

    The impact of subchorionic hematoma in the first trimester on maternal and neonatal outcomes in singleton pregnancies · 2026 · DOI

  • international practice. Pregnancy Hypertens. 2018;13:291-310 the Study of Hypertension classification, diagnosis for 7. Predictive value of angiogenic factors, clinical risk factors and uterine artery Doppler for pre-eclampsia and fetal growth restriction in second and third trimester pregnancies in an Ecuadorian population. J Matern Fetal Neonatal Med. 2016;29(4):537-43. 8. Graupner O, Karge A, Flechsenhar S, Seiler A, Haller B, Ortiz JU, Lobmaier SM, Axt-Fliedner R, Enzensberger C, Abel K, Kuschel B. Role of sFlt-1/PlGF ratio and feto-maternal Doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia. Arch Gynecol Obstet. 2020;301(2):375-385. 9. Fishel Bartal M, Lindheimer MD, Sibai BM. Proteinuria during pregnancy: definition, pathophysiology, methodology, and Gynecol.

    Predictive Value of Proteinuria at the Time of IUGR Diagnosis for the Development of Preeclampsia or Gestational Hypertension · 2026 · DOI

  • the development The major strengths of this study include its relatively large, well-defined IUGR cohort and the dual two standardized assessment of proteinuria by methods. The inclusion of only normotensive women at baseline allows for clearer interpretation of proteinuria as a predictive rather than diagnostic variable. However, certain limitations should be acknowledged. The retrospective design introduces potential selection and measurement bias. The study did not control for all confounding variables such as maternal renal function markers (e.g., serum creatinine, uric acid) or angiogenic factor levels, which could have enhanced mechanistic understanding. Another limitation was the lack of complete information on low-dose aspirin use at the time of IUGR diagnosis, which could have influenced of subsequent hypertensive disorders. In addition, the absence of a longitudinal follow-up on postpartum outcomes limits the extrapolation of results to long-term maternal cardiovascular risk. Prospective multicenter studies integrating biochemical and Doppler parameters are warranted these findings and refine prediction algorithms. In summary, that proteinuria detected at the time of IUGR diagnosis, whether by 24-hour urine protein measurement or spot Pr/Cr ratio, is a significant predictor of subsequent preeclampsia or gestational hypertension. The strong later association between early proteinuria and shared hypertensive placental between pathophysiologic dysfunction and maternal vascular injury. Given its accessibility and predictive power, routine assessment of proteinuria in IUGR pregnancies could serve as a simple yet valuable tool for early risk stratification and individualized antenatal surveillance. this study provides evidence underscores to validate continuum disease the Researcher Contribution Statement: Idea and design: S.E.Y, N.N; Data collection and processing: S.E.Y, N.N; Analysis and interpretation of data: S.E.Y, N.N; Writing of significant parts of the article: S.E.Y; Review and editing: S.E.Y. 1804251 S. Eriş Yalçın and N. Nerez Support and Acknowledgement Statement: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

    Predictive Value of Proteinuria at the Time of IUGR Diagnosis for the Development of Preeclampsia or Gestational Hypertension · 2026 · DOI

  • This study recommends strengthening comprehensive antenatal care with emphasis on gestational age and maternal nutritional status as key indicators of neonatal adaptation risk. Early screening should be prioritized to detect pregnancies at risk of low Apgar scores, particularly in mothers with abnormal BMI. Future research is encouraged to include additional confounding factors such as mode of delivery, intrapartum conditions, and placental factors to improve predictive accuracy. Longitudinal or cohort designs are also recommended to strengthen causal inference regarding determinants of neonatal Apgar scores.

    Maternal Hemodynamic and Nutritional Determinants of Neonatal Apgar score: The Role of Gestational Age, Body Mass Index, Hemoglobin, and Mean Arterial Pressure · 2026 · DOI

  • The study was limited by its small sample size and short duration, restricting the statistical power and generalizability of findings. Some patients had coexisting medical disorders, which may have confounded the correlation between specific placental changes and individual conditions. Additionally, quantitative morphometric analysis and immunohistochemical correlation were not performed, which could have provided deeper insights into the pathophysiological mechanisms involved.

    Clinical Correlation of Placental Pathology in Medical Disorders of Pregnancy and Its Comparison in Normal Pregnancy · 2026 · DOI

  • The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined.

    Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort · 2026 · DOI

  • Recent findings The timing and threshold for antihypertensive initiation remain controversial, but recent evidence supports the treatment of chronic hypertension targeted to a blood pressure (BP) of less than 140/90 mmHg.

    Management of hypertensive disorders in pregnancy · 2026 · DOI

  • EV‐derived cargo was detected in cells on the abluminal side of the endothelial layer, suggesting possible transfer across the barrier, although the underlying mechanism remains unclear.

    Preeclampsia‐derived small extracellular vesicles disrupt blood–brain barrier integrity and activate glial cells <i>in vitro</i> · 2026 · DOI

  • Future research should focus on elucidating these pathways to develop more targeted therapeutic interventions (25, 26). Future research should focus on large-scale, well- designed studies that standardize lipid assessment methods and consider confounding factors to further elucidate the bidirectional relationship between lipid metabolism and PE.

    Association between blood lipid levels and preeclampsia: a meta-analysis · 2026 · DOI

  • This study utilizes a retrospective cohort design, which may introduce bias due to its reliance on existing medical records. The accuracy and completeness of the collected data could be compromised, leading to potential misclassification of cases or incomplete information. Additionally, the research was conducted at only two hospitals, which may restrict the generalizability of the findings. Differences in clinical practices, diagnostic criteria, and patient demographics across various institutions could influence the results, limiting their applicability to broader populations.

    Hypoalbuminemia as a severity predictor of preeclampsia in a multicenter study from Indonesia · 2026 · DOI

  • for • Preeclampsia is gestational hypertension accompanied by ≥1 new-onset conditions at or after 20 weeks’ gestation. Eclampsia is defined as seizures in a pregnant woman with preeclampsia with no other identifiable cause. Preeclampsia and eclampsia are classified in the same category (preeclampsia-eclampsia, PE). • Chronic hypertension (CH) refers to high BP predating the pregnancy or recognized at <20 weeks’ gestation. • Gestational hypertension (GH) is persistent de novo hypertension that develops at or after 20 weeks’ gestation in the absence of features of preeclampsia. • Chronic hypertension with superimposed preeclampsia (CHSP) is chronic hypertension with development of new proteinuria and/or organ or uteroplacental dysfunction(s). In this study, the APOs included anemia, diabetes mellitus, preterm birth, low birthweight, hemorrhage disorder, infection, liver disease, stillbirth and neonatal death, maternal near-miss, kidney disease, heart disease, pulmonary disease, embolism, and maternal death. The definitions of the above APOs were consistent with the WHO standards (17, 18). 2.3 Ethics approval and consent to participate The Medical Ethics Committee of Hunan Provincial Maternal and Child Health Care Hospital approved the study (NO: 2024-S155). The Hunan Provincial Health Commission routinely collected surveillance data, and the government has developed the “Maternal Near Miss Surveillance Working Manual” to collect those data. It is a retrospective study of medical records; all data were fully anonymized before we accessed them. Moreover, we de-identified the patient records before analysis. Since the Government routinely collects these data, the need for informed consent to participate was waived. We confirmed that all operations were following relevant guidelines and regulations.

    Adverse pregnancy outcomes in hypertensive disorders of pregnancy: an in-depth comparison between subtypes · 2026 · DOI

  • Some things could be improved in this study. First, we cannot determine whether there is a causal association between HDP and APOs or whether there were other confounding factors. Second, long-term APOs were not included due to data limita- tions. Third, most of the mechanisms are still unknown. Future in-depth studies are needed. Fourth, the study population were come from a province in China; although the sample size was large, the study nevertheless had limitations in terms of the restricted ethno-sociodemographic characteristics of the study population.

    Adverse pregnancy outcomes in hypertensive disorders of pregnancy: an in-depth comparison between subtypes · 2026 · DOI

  • This study had some limitations as well. The study was conducted in a single tertiary hospital. So, the result of the study may not be reflecting the exact status of the population. Study sample was limited and could not be increase due to financial constraints. Other factors that might have disrupted placental function and perfusion, vascular endothelial stress marker dysfunction, interact with PE were not investigated. Therefore, the study findings cannot be generalized to the entire population. resistance, oxidative REFERENCES 1. Grotegut CA. Prevention of preeclampsia. J Clin Invest. 2016;126(12):4396-4398.

    Association of Serum CA-125 with Preeclampsia in a Tertiary Care Hospital · 2026 · DOI

  • Third, the sFlt−1/PlGF ratio was measured using a single commercial assay platform, and the generalizability of the FAR−enhanced model to other assay systems remains to be established. resource allocation would be of considerable clinical Second, the optimal threshold of FAR for clinical decision −making remains to be established. Several limitations of this study should be acknowledged.

    Incremental prognostic value of the fibrinogen−to−albumin ratio for adverse perinatal outcomes in preeclampsia: a dual−center retrospective cohort study · 2026 · DOI

  • Novel symptoms associated with eclampsia could improve detection and save lives Alice Beardmore-Gray *, Andrew Shennan Department of Women and Children’s Health, King’s College London, London, United Kingdom * [email protected] A woman dies every 2 min during pregnancy or childbirth. Hypertensive disorders of pregnancy, including pre-eclampsia, are the leading direct cause after postpartum hemorrhage. Of these deaths, 95% occur in low- and middle-income countries (LMICs), and the regions of sub-Saharan Africa and South Asia account for 87% of all global maternal deaths. This stark inequality is projected to deepen over the next decade, as funding scarcity, conflict, climate change, and a shifting geopolitical landscape threaten hard-won gains in women’s health. Pre-eclampsia, a multi-system endothelial disorder caused by placental dysfunction, is progressive, and the onset of severe features is difficult to predict. This is especially true in low-resource contexts where limited access to laboratory testing and obstetric ultrasound is further compounded by health workforce shortages, resulting in a lack of adequate surveillance for women at high-risk of complications and poor quality care. Eclampsia is a manifestation of severe pre-eclampsia with an associated mortality rate of up to 7%. It is frequently associated with additional complications including intracerebral hemorrhage, pulmonary oedema, placental abruption, and stillbirth. Current management includes administration of magnesium sulfate, which more than halves the risk of eclampsia and is indicated for both primary prevention and recurrence. It should be given to all women who have severe pre-eclampsia or eclampsia, whether antenatal or postnatal, and is recognized by the World Health Organization and United Nations to be a priority drug. While its exact mechanism of action is unknown, it is thought to prevent and control seizures by stabilizing neuronal networks and reducing cerebral vasospasm and ischemia. Understanding which women with pre-eclampsia are most at risk of progressing to eclampsia and other severe complications is critical to informing women’s and clinicians’ decision-making and guiding clinical management. While stabilizing blood pressure is important, delivery is currently the only intervention shown to reduce the risk of adverse maternal outcomes and fetal death, and should be recommended immediately if severe features, including eclampsia, develop. Accurately triaging women to identify those most at risk, in order to optimize timing of birth, with consideration of antenatal corticosteroids if delivery is planned prior to 34 weeks’ gestation, remains a critical challenge.

    Novel symptoms associated with eclampsia could improve detection and save lives · 2026 · DOI

  • Future research should focus on validating these hemodynamic markers in larger, diverse populations to further enhance predic- tive precision.

    Development and validation of a machine learning model for predicting hypertensive disorders of pregnancy based on fetal aortic hemodynamic parameters · 2026 · DOI

  • The mechanistic link between cerebral autoregulation dysfunction and systemic cardiovascular responses through altered autonomic control is proposed but lacks direct experimental evidence establishing the causal direction and the specific brainstem or hypothalamic circuits mediating this neuro-immune-cardiovascular axis in preeclampsia.

    The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation · 2026 · DOI

  • The prediction that individuals with heightened baseline neuroimmune or autonomic sensitivity show greater neurological vulnerability to placental stressors lacks operationalized criteria for identifying or measuring 'baseline neuroimmune sensitivity' or 'autonomic robustness' in prospective cohorts, and does not specify which cellular or molecular immune markers should define this vulnerability phenotype.

    The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation · 2026 · DOI

  • The paper identifies that different preeclampsia subtypes (acute neurovascular instability versus placental angiogenic dysfunction) should exhibit distinct autonomic imbalance signatures, but does not specify which standardized autonomic biomarkers should be measured (heart rate variability indices, baroreceptor sensitivity, sympathetic/parasympathetic tone ratios) or establish cutoff thresholds for distinguishing PE subtypes.

    The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation · 2026 · DOI

  • The paper proposes that targeted modulation of central autonomic or sensory integration circuits may reduce neurological manifestations such as eclampsia or cerebral autoregulation failure in preclinical models, but does not specify which circuit targets (e.g., nucleus tractus solitarius, dorsal motor nucleus, insular cortex) should be prioritized or what modulation techniques (optogenetics, chemogenetics, pharmacological interventions) should be tested.

    The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation · 2026 · DOI

  • The relatively small sample size in each group may limit the generalizability of the findings. Second, the cross- sectional design precludes assessment of temporal rela- tionships and long-term perinatal outcomes, preventing causal inferences. Potential confounding factors may also have influenced Mod-MPI measurements. The relatively wide gestational age range (20–38 weeks), although Mod-MPI is consid- ered relatively gestational-age independent, may still have introduced variability that was not adjusted for sta- tistically. In addition, maternal factors such as body mass index, degree of glycemic control, severity and onset of preeclampsia, and medication use (e.g., insulin or antihy- pertensive therapy) were not stratified or controlled for, which may have influenced fetal cardiac function. Furthermore, decreased fetal perception was based on subjective maternal reporting and may be subject to recall bias. Although all measurements were performed by a single experienced blinded operator using a stand- ardized protocol, formal intra-observer reproducibility analysis was not conducted. Finally, the absence of adjust- ment for potential hemodynamic and biochemical con- founders limits the ability to fully isolate the independent effect of GDM and preeclampsia on Mod-MPI. Future prospective longitudinal studies with larger cohorts and multivariate analysis are needed to better control for these confounders and clarify the independ- ent predictive value of Mod-MPI.

    Modified myocardial performance index (Mod-MPI) as a Doppler-derived marker for fetal cardiac dysfunction in diabetic and preeclamptic pregnancies · 2026 · DOI

  • Scant information exists for use of NGAL determination in children only with asthma, sepsis and kidney diseases, with limited pediatric applications documented.

    Early pregnancy pre-eclampsia screening using Fetal Medicine Foundation formula: a longitudinal study · 2025 · DOI

  • When considering our findings alongside existing literature, it remains inconclusive whether the serum thiol-disulfide ratio can predict a healthy pregnancy or MA following AI.

    Predictive effect of thiol/disulfide homeostasis dynamics on early pregnancy viability: A case-control study · 2024 · DOI

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92 open questions have been extracted from the limitations and future-work passages of 848 Pregnancy and preeclampsia studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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