Medicine › Obstetrics and Gynecology

Pregnancy and preeclampsia studies

Works Count: 113150

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Description

This cluster of papers focuses on the pathophysiology, risk factors, diagnosis, and management of preeclampsia, including its association with placental development, hypertensive disorders, endothelial dysfunction, maternal mortality, fetal growth restriction, angiogenic factors, oxidative stress, and long-term cardiovascular health implications for both mothers and offspring.

Keywords

Preeclampsia; Placental Development; Hypertensive Disorders; Endothelial Dysfunction; Maternal Mortality; Fetal Growth Restriction; Angiogenic Factors; Oxidative Stress; Cardiovascular Health; Pregnancy Complications

Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study Pre-eclampsia and cardiovascular disease later in life: who is at risk?

2001-11-24

Henrik Irgens , Lars Reisater , Lorentz M. Irgens +2 more

<h3>Abstract</h3> <b>Objective:</b> To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. <b>Design:</b> Population … <h3>Abstract</h3> <b>Objective:</b> To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. <b>Design:</b> Population based cohort study of registry data. <b>Subjects:</b> Mothers and fathers of all 626 272 births that were the mothers9 first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies. <b>Main outcome measures:</b> Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death. <b>Results:</b> Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur. <b>Conclusions:</b> Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers. <h3>What is already known on this topic</h3> Maternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnancies One set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother9s risk of death from cardiovascular disease <h3>What this study adds</h3> Women who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to term Fathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular disease These results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease

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Onset of Maternal Arterial Blood Flow and Placental Oxidative Stress

2000-12-01

Eric Jauniaux , Adrian Watson , Joanne Hempstock +3 more

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Estimation of fetal weight with the use of head, body, and femur measurements—A prospective study

1985-02-01

Frank P. Hadlock , Ronald B. Harrist , Ralph S. Sharman +2 more

Syndrome of hemolysis, elevated liver enzymes, and low platelet count: A severe consequence of hypertension in pregnancy

1982-01-01

Louis Weinstein

The Uterine Spiral Arteries In Human Pregnancy: Facts and Controversies

2006-02-22

Robert Pijnenborg , L. Vercruysse , M. Hanssens

Preeclampsia: An endothelial cell disorder

1989-11-01

James Roberts , Robert N. Taylor , Thomas J. Musci +3 more

Pre-eclampsia: more than pregnancy-induced hypertension

1993-06-01

James M. Roberts , Christopher W.G. Redman

Latest Advances in Understanding Preeclampsia

2005-06-09

Christopher W.G. Redman , Ian L. Sargent

Preeclampsia is a relatively common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both … Preeclampsia is a relatively common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both mother and baby. We summarize recent work on the causes of preeclampsia, which reveals a new mode of maternal immune recognition of the fetus, relevant to the condition. The circulating factors derived from the placenta, which contributes to the clinical syndrome, are now better understood. This brief review on preeclampsia does not cover all aspects of this intriguing condition but focuses on some new and interesting findings.

Pathogenesis and genetics of pre-eclampsia

2001-01-01

JM Roberts , DW Cooper

The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP

2014-02-15

A. L. Tranquilli , G. Dekker , Laura A. Magee +5 more

Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome)

1993-10-01

Baha M. Sibai , Mohammed K. Ramadan , Ihab M. Usta +3 more

A Study of Angiotensin II Pressor Response throughout Primigravid Pregnancy

1973-11-01

Norman F. Gant , Gilroy L. Daley , Santosh Chand +2 more

The present study was designed to ascertain sequentially the pressor response to angiotensin II in young primigravid patients throughout pregnancy in order a) to define when in pregnancy resistance to … The present study was designed to ascertain sequentially the pressor response to angiotensin II in young primigravid patients throughout pregnancy in order a) to define when in pregnancy resistance to the pressor effects of angiotensin II develops; b) to define the physiologic sequence of events leading to this resistance; and c) to ascertain whether sensitivity to infused angiotensin II could be detected before the onset of clinical signs of pregnancy-induced hypertension. With this prospective approach, two separate groups of patients were defined. The first group of patients remained normal throughout pregnancy. The second group consisted of those patients who, while clinically normotensive during the initial phase of the study, ultimately developed hypertension of pregnancy.192 patients were studied; of these, 120 patients remained normotensive and 72 developed pregnancy-induced hypertension. In both groups, vascular resistance to infused angiotensin II (more than 8 ng/kg/min required to elicit a pressor response of 20 mm Hg in diastolic pressure) was demonstrated as early as the 10th wk of pregnancy. In the group that remained normotensive, maximum mean vascular resistance occurred at 18-30 wk of pregnancy, (mean pressor dose required being 13.5 to 14.9 ng/kg/min). In those subjects who developed pregnancy-induced hypertension, the mean maximum dose required was 12.9 ng/kg/min, which was observed at the 18th wk of pregnancy. By the 22nd wk there was a clear separation of the two groups, with the mean dose requirement of the subjects destined to develop hypertension being progressively less than that of those who remained normal. The difference between the two groups became significant (P < 0.01) by 23-26 wk of pregnancy. Among patients requiring more than 8 ng/kg/min on one or more tests done between wk 28-32, 91% remained normotensive. Conversely, during the same time period among patients requiring less than 8 ng/kg/min, on at least one occasion, 90% developed pregnancy-induced hypertension.

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Rheological and Physiological Consequences of Conversion of the Maternal Spiral Arteries for Uteroplacental Blood Flow during Human Pregnancy

2009-04-18

Graham J. Burton , Allison Woods , Eric Jauniaux +1 more

Physiological conversion of the maternal spiral arteries is key to a successful human pregnancy. It involves loss of smooth muscle and the elastic lamina from the vessel wall as far … Physiological conversion of the maternal spiral arteries is key to a successful human pregnancy. It involves loss of smooth muscle and the elastic lamina from the vessel wall as far as the inner third of the myometrium, and is associated with a 5-10-fold dilation at the vessel mouth. Failure of conversion accompanies common complications of pregnancy, such as early-onset preeclampsia and fetal growth restriction. Here, we model the effects of terminal dilation on inflow of blood into the placental intervillous space at term, using dimensions in the literature derived from three-dimensional reconstructions. We observe that dilation slows the rate of flow from 2 to 3m/s in the non-dilated part of an artery of 0.4-0.5mm diameter to approximately 10 cm/s at the 2.5mm diameter mouth, depending on the exact radius and viscosity. This rate predicts a transit time through the intervillous space of approximately 25s, which matches observed times closely. The model shows that in the absence of conversion blood will enter the intervillous space as a turbulent jet at rates of 1-2m/s. We speculate that the high momentum will damage villous architecture, rupturing anchoring villi and creating echogenic cystic lesions as evidenced by ultrasound. The retention of smooth muscle will also increase the risk of spontaneous vasoconstriction and ischaemia-reperfusion injury, generating oxidative stress. Dilation has a surprisingly modest impact on total blood flow, and so we suggest the placental pathology associated with deficient conversion is dominated by rheological consequences rather than chronic hypoxia.

Evaluation of High-Sensitivity C-Reactive Protein and Serum Lipid Profile in Southeastern Nigerian Women with Pre-Eclampsia

2015-01-01

Anaelechi J. Onuegbu , Japhet M. Olisekodiaka , John U. Udo +4 more

The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors … The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors conducted a nested case-control study of 55 preeclamptic women and 165 pregnant controls from the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001). Serum samples collected at < or = 20 weeks' gestation were analyzed for levels of C-reactive protein and triglycerides. The adjusted odds ratio (AOR) from a multivariable conditional logistic regression model assessing the total effect of body mass index on preeclampsia risk was compared with the AOR from the same model after results were controlled for C-reactive protein, triglycerides, and confounding factors (direct-effects model). The percentage of the total effect that was mediated through inflammation and triglycerides was calculated as 100 - [ln(direct-effects AOR)/ln(total-effects AOR)]. In the total-effects model, 4- and 8-unit increases in body mass index were associated with 1.7-fold (95% confidence interval (CI): 1.3, 2.3) and 2.9-fold (95% CI: 1.6, 5.2) increases in preeclampsia risk, whereas in the direct-effects model, these AORs were 1.4 (95% CI: 1.0, 1.9) and 2.0 (95% CI: 1.0, 3.8), respectively. Inflammation was a more important mediator than triglycerides. These findings suggest that approximately one third of the total effect of body mass index on preeclampsia risk is mediated through inflammation and triglyceride levels.

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Intrauterine growth curves based on ultrasonically estimated foetal weights

1996-07-01

K. Maršál , P‐H. Persson , Torben Larsen +3 more

Available standard intrauterine growth curves based on birthweights underestimate foetal growth in preterm period. New growth curves are presented based on data from four Scandinavian centres for 759 ultrasonically estimated … Available standard intrauterine growth curves based on birthweights underestimate foetal growth in preterm period. New growth curves are presented based on data from four Scandinavian centres for 759 ultrasonically estimated foetal weights in 86 uncomplicated pregnancies. Mean weight of boys exceeded that of girls by 2‐3%. A uniform SD value of 12% of the mean weight was adopted for the standard curves as the true SD varied non‐systematically between 9.1 and 12.4%. Applied to an unselected population of 8663 singleton births, before 210 days of gestation, 32% of birthweights were classified as small‐for‐gestational age (SGA; i.e. below mean ‐2SD); the corresponding figures were 11.1% for gestational ages between 210 and 258 days, and 2.6% for ages of 259 days or longer. The new growth curves reveal better the true distribution of SGA foetuses and neonates, and are suggested for use in perinatological practice.

The “Great Obstetrical Syndromes” are associated with disorders of deep placentation

2010-11-21

Ivo Brosens , Robert Pijnenborg , Lisbeth Vercruysse +1 more

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In utero analysis of fetal growth: a sonographic weight standard.

1991-10-01

F P Hadlock , R B Harrist , Juan Martinez‐Poyer

Regression analysis was used to develop an in utero fetal weight model from a population of 392 predominantly middle-class white patients with certain menstrual histories. There was a gradual increase … Regression analysis was used to develop an in utero fetal weight model from a population of 392 predominantly middle-class white patients with certain menstrual histories. There was a gradual increase in fetal weight from 35 g at 10 weeks to 3,619 g at 40 weeks, with uniform variance of +/- 12.7% (1 standard deviation) throughout gestation. When tested against the estimated weights of 1,771 chromosomally normal fetuses between 14 and 21 weeks, the mean percent difference was 0.8% and the average absolute percent error was 3.3%. When compared with actual delivery data for 163 fetuses in the group, the mean percent difference was 0.8% and the average absolute percent error was 1.1%. These data are compared with other prenatal weight curves obtained at ultrasound and with data from several large postnatal weight studies.

Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis

2007-11-01

Leanne Bellamy , Juan-Pablo Casas , Aroon D. Hingorani +1 more

<b>Objective</b> To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Embase and Medline without language restrictions, including papers published … <b>Objective</b> To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports. <b>Review methods</b> Prospective and retrospective cohort studies were included, providing a dataset of 3 488 160 women, with 198 252 affected by pre-eclampsia (exposure group) and 29 495 episodes of cardiovascular disease and cancer (study outcomes). <b>Results</b> After pre-eclampsia women have an increased risk of vascular disease. The relative risks (95% confidence intervals) for hypertension were 3.70 (2.70 to 5.05) after 14.1 years weighted mean follow-up, for ischaemic heart disease 2.16 (1.86 to 2.52) after 11.7 years, for stroke 1.81 (1.45 to 2.27) after 10.4 years, and for venous thromboembolism 1.79 (1.37 to 2.33) after 4.7 years. No increase in risk of any cancer was found (0.96, 0.73 to 1.27), including breast cancer (1.04, 0.78 to 1.39) 17 years after pre-eclampsia. Overall mortality after pre-eclampsia was increased: 1.49 (1.05 to 2.14) after 14.5 years. <b>Conclusions</b> A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women. This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both. No association was found between pre-eclampsia and future cancer.

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The Global Impact of Pre-eclampsia and Eclampsia

2009-05-22

Lelia Duley

A CRITICAL EVALUATION OF SONAR “CROWN‐RUMP LENGTH” MEASUREMENTS

1975-09-01

Hugh P. Robinson , J. E. E. Fleming

In a study to evaluate the reproducibility and accuracy of the sonar technique of measurement of the in vivo fetal crown-rump length (Robinson, 1973), a series of in vivo and … In a study to evaluate the reproducibility and accuracy of the sonar technique of measurement of the in vivo fetal crown-rump length (Robinson, 1973), a series of in vivo and in vitro experiments was performed in which the random and systematic errors inherent in the technique were assessed. The potential sources of random error were those of operator judgement, movement of the fetus and mother, machine sensitivity settings and measurement from the photograph; while the sources of systematic error were those of oscilloscope scale factor, and velocity calibration inaccuracies, and the effect of beam width. The overall effect of the random errors, that is, the reproducibility of the technique, was assessed in an in vivo blind trial in which three independent measurements were made of the fetus. In a series of 30 experiments the average standard deviation of the three readings was found to be 1.2 mm. Evaluation of the systematic errors by in vivo experimentation, on the other hand, showed that the basic sonar measurements were in error by an overestimate of 1 mm for the beam width effect and 3.7 per cent for the scale factor and velocity calibration errors. A weighted non-linear regression analysis of 334 measurements was performed in order to obtain a "curve of best fit" for the period covering 6 to 14 weeks of menstrual age. The values obtained were corrected for the systematic errors and compared with widely quoted anatomical figures. In the second part of this investigation the original data was further analyzed to determine on a statistical basis the accuracy of the technique as a method of estimating maturity. It was shown that such an estimate could be made to within 4.7 days with a 95 per cent probability on the basic of a single measurement, and to within 2.7 days if three independent measurements were made.

Global and regional estimates of preeclampsia and eclampsia: a systematic review

2013-06-06

Edgardo Ábalos , Cristina Cuesta , Ana L. Grosso +2 more

Preeclampsia: An excessive maternal inflammatory response to pregnancy

1999-02-01

Christopher W.G. Redman , Gavin Sacks , Ian L. Sargent

Soluble endoglin contributes to the pathogenesis of preeclampsia

2006-06-01

Shivalingappa Venkatesha , Mourad Toporsian , Chun Sing Lam +7 more

Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis

2011-04-01

Vicki Flenady , Laura Koopmans , Philippa Middleton +7 more

Inadequate maternal vascular response to placentation in pregnancies complicated by pre‐eclampsia and by small‐for‐gestational age infants

1986-10-01

T. Yee Khong , Frank de Wolf , W.B. Robertson +1 more

Summary. An examination of the maternal vascular response to placentation shows that physiological changes in the placental bed normally extend from the decidua into the inner myometrium. In pre‐eclampsia and … Summary. An examination of the maternal vascular response to placentation shows that physiological changes in the placental bed normally extend from the decidua into the inner myometrium. In pre‐eclampsia and in a proportion of pregnancies with small‐for‐gestational age infants (SGA) the physiological changes are restricted to the decidual segments alone. In addition, complete absence of physiological changes throughout the entire length of some spiral arteries is seen in pre‐eclampsia and SGA. This new observation is confirmed in a study of basal plates of placentas from abnormal pregnancies. Intraluminal endovascular trophoblast may be seen in the placental bed spiral arteries in the third trimester in pre‐eclampsia and SGA, a feature not seen beyond the second trimester in normal pregnancy. These findings point to a defect in the normal interaction between migratory trophoblast and maternal uterine tissues in pre‐eclampsia and in SGA.

Major Congenital Malformations after First-Trimester Exposure to ACE Inhibitors

2006-06-07

William O. Cooper , Sonia Hernández–Dı́az , Patrick G. Arbogast +5 more

Use of angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy is contraindicated because of their association with an increased risk of fetopathy. In contrast, first-trimester use of … Use of angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy is contraindicated because of their association with an increased risk of fetopathy. In contrast, first-trimester use of ACE inhibitors has not been linked to adverse fetal outcomes. We conducted a study to assess the association between exposure to ACE inhibitors during the first trimester of pregnancy only and the risk of congenital malformations.We studied a cohort of 29,507 infants enrolled in Tennessee Medicaid and born between 1985 and 2000 for whom there was no evidence of maternal diabetes. We identified 209 infants with exposure to ACE inhibitors in the first trimester alone, 202 infants with exposure to other antihypertensive medications in the first trimester alone, and 29,096 infants with no exposure to antihypertensive drugs at any time during gestation. Major congenital malformations were identified from linked vital records and hospitalization claims during the first year of life and confirmed by review of medical records.Infants with only first-trimester exposure to ACE inhibitors had an increased risk of major congenital malformations (risk ratio, 2.71; 95 percent confidence interval, 1.72 to 4.27) as compared with infants who had no exposure to antihypertensive medications. In contrast, fetal exposure to other antihypertensive medications during only the first trimester did not confer an increased risk (risk ratio, 0.66; 95 percent confidence interval, 0.25 to 1.75). Infants exposed to ACE inhibitors were at increased risk for malformations of the cardiovascular system (risk ratio, 3.72; 95 percent confidence interval, 1.89 to 7.30) and the central nervous system (risk ratio, 4.39; 95 percent confidence interval, 1.37 to 14.02).Exposure to ACE inhibitors during the first trimester cannot be considered safe and should be avoided.

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Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia

2003-03-01

Sharon E. Maynard , Jiang-Yong Min , Jaime R. Merchan +7 more

Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is … Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. We demonstrate that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia.

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THE CLASSIFICATION AND DIAGNOSIS OF THE HYPERTENSIVE DISORDERS OF PREGNANCY: STATEMENT FROM THE INTERNATIONAL SOCIETY FOR THE STUDY OF HYPERTENSION IN PREGNANCY (ISSHP)

2001-01-01

Mark Brown , Marshall D. Lindheimer , Michael de Swiet +2 more

(2001). The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP) Hypertension in Pregnancy: Vol. 20, No. … (2001). The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP) Hypertension in Pregnancy: Vol. 20, No. 1, pp. ix-xiv.

Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies

2005-03-02

Kirsten Duckitt , Deborah J. Harrington

<h3>Abstract</h3> <b>Objective</b> To determine the risk of pre-eclampsia associated with factors that may be present at antenatal booking. <b>Design</b> Systematic review of controlled studies published 1966-2002. <b>Data synthesis</b> Unadjusted relative … <h3>Abstract</h3> <b>Objective</b> To determine the risk of pre-eclampsia associated with factors that may be present at antenatal booking. <b>Design</b> Systematic review of controlled studies published 1966-2002. <b>Data synthesis</b> Unadjusted relative risks were calculated from published data. <b>Results</b> Controlled cohort studies showed that the risk of pre-eclampsia is increased in women with a previous history of pre-eclampsia (relative risk 7.19, 95% confidence interval 5.85 to 8.83) and in those with antiphospholipids antibodies (9.72, 4.34 to 21.75), pre-existing diabetes (3.56, 2.54 to 4.99), multiple (twin) pregnancy (2.93, 2.04 to 4.21), nulliparity (2.91, 1.28 to 6.61), family history (2.90, 1.70 to 4.93), raised blood pressure (diastolic ≥ 80 mm Hg) at booking (1.38, 1.01 to 1.87), raised body mass index before pregnancy (2.47, 1.66 to 3.67) or at booking (1.55, 1.28 to 1.88), or maternal age ≥ 40 (1.96, 1.34 to 2.87, for multiparous women). Individual studies show that risk is also increased with an interval of 10 years or more since a previous pregnancy, autoimmune disease, renal disease, and chronic hypertension. <b>Conclusions</b> These factors and the underlying evidence base can be used to assess risk at booking so that a suitable surveillance routine to detect pre-eclampsia can be planned for the rest of the pregnancy.

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Purification, Characterization, and<i>in vitro</i>Differentiation of Cytotrophoblasts from Human Term Placentae*

1986-04-01

Harvey J. Kliman , John E. Nestler , EDUARDO SERMASI +2 more

Highly purified functional cytotrophoblasts have been prepared from human term placentae by adding a Percoll gradient centrifugation step to a standard trypsin-DNase dispersion method. The isolated mononuclear trophoblasts averaged 10 … Highly purified functional cytotrophoblasts have been prepared from human term placentae by adding a Percoll gradient centrifugation step to a standard trypsin-DNase dispersion method. The isolated mononuclear trophoblasts averaged 10 μm in diameter, with occasional cells measuring up to 20–30 μm. Viability was greater than 90%. Transmission electron microscopy revealed that the cells had fine structural features typical of trophoblasts. In contrast to syncytial trophoblasts of intact term placentae, these cells did not stain for hCG, human placental lactogen, pregnancy-specific α1-glycoprotein or low mol wt cytokeratins by immunoperoxidase methods. Endothelial cells, fibroblasts, or macrophages did not contaminate the purified cytotrophoblasts, as evidenced by the lack of immunoperoxidase staining with antibodies against vimentin or α1-antichymotrypsin. The cells produced progesterone (1 ng/106 cells-4 h), and progesterone synthesis was stimulated up to 8- fold in the presence of 25-hydroxycholesterol (20 μg/ml). They also produced estrogens (1360 pg/106 cells-4 h) when supplied with androstenedione (1 ng/ml) as a precursor. When placed in culture, the cytotrophoblasts consistently formed aggregates, which subsequently transformed into syncytia within 24–48 h after plating. Time lapse cinematography revealed that this process occurred by cell fusion. The presumptive syncytial groups were proven to be true syncytia by microinjection of fluorescently labeled y9-actinin, which diffused completely throughout the syncytial cytoplasm within 30 min. Immunoperoxidase staining of cultured trophoblasts between 3.5 and 72 h after plating revealed a progressive increase in cytoplasmic pregnancy-specific β1-glycoprotein, hCG, and human placental lactogen concomitant with increasing numbers of aggregates and syncytia. At all time points examined, occasional single cells positive for these markers were identified. RIA of the spent culture media for hCG revealed a significant increase in secreted hCG, paralleling the increase in hCG-positive cells and syncytia identified by immunoperoxidase methods. We conclude that human cytotrophoblasts differentiate in culture and fuse to form functional syncytiotrophoblasts. {Endocrinology118:1567–1582,1986)

Endovascular Trophoblast Invasion: Implications for the Pathogenesis of Intrauterine Growth Retardation and Preeclampsia

2003-07-01

Peter Kaufmann , Simon Black , Berthold Huppertz

Maternal uteroplacental blood flow increases during pregnancy. Altered uteroplacental blood flow is a core predictor of abnormal pregnancy. Normally, the uteroplacental arteries are invaded by endovascular trophoblast and remodeled into … Maternal uteroplacental blood flow increases during pregnancy. Altered uteroplacental blood flow is a core predictor of abnormal pregnancy. Normally, the uteroplacental arteries are invaded by endovascular trophoblast and remodeled into dilated, inelastic tubes without maternal vasomotor control. Disturbed remodeling is associated with maintenance of high uteroplacental vascular resistance and intrauterine growth restriction (IUGR) and preeclampsia. Herein, we review routes, mechanisms, and control of endovascular trophoblast invasion. The reviewed data suggest that endovascular trophoblast invasion involves a side route of interstitial invasion. Failure of vascular invasion is preceded by impaired interstitial trophoblast invasion. Extravillous trophoblast synthesis of nitric oxide is discussed in relation to arterial dilation that paves the way for endovascular trophoblast. Moreover, molecular mimicry of invading trophoblast-expressing endothelial adhesion molecules is discussed in relation to replacement of endothelium by trophoblast. Also, maternal uterine endothelial cells actively prepare endovascular invasion by expression of selectins that enable trophoblast to adhere to maternal endothelium. Finally, the mother can prevent endovascular invasion by activated macrophage-induced apoptosis of trophoblast. These data are partially controversial because of methodological restrictions associated with limitations of human tissue investigations and animal studies. Animal models require special care when extrapolating data to the human due to extreme species variations regarding trophoblast invasion. Basal plates of delivered placentas or curettage specimens have been used to describe failure of trophoblast invasion associated with IUGR and preeclampsia; however, they are unsuitable for these kinds of studies, since they do not include the area of pathogenic events, i.e., the placental bed.

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Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial

2002-06-01

Douglas G. Altman , Guillermo Carroli , Lelia Duley +4 more

Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

2016-01-06

Harald Zeisler , Elisa Llurba , Frédéric Chantraine +7 more

The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in … The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear.We performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks.In the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3).An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).

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Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement

2016-05-25

T. Yee Khong , Eoghan E. Mooney , Ilana Ariel +7 more

-The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories.-To establish an agreed-upon protocol for sampling the placenta, and … -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories.-To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community.-Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible.-The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

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Physiological changes in pregnancy

2016-05-18

Priya Soma‐Pillay , Catherine Nelson‐Piercy , Heli Tolppanen +1 more

Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery.Some of these changes influence normal biochemical values while others may mimic symptoms … Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery.Some of these changes influence normal biochemical values while others may mimic symptoms of medical disease.It is important to differentiate between normal physiological changes and disease pathology.This review highlights the important changes that take place during normal pregnancy.

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Consensus definition of fetal growth restriction: a Delphi procedure

2016-02-25

Sanne J. Gordijn , Irene Beune , B. Thilaganathan +6 more

Objective To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. Method A Delphi survey was conducted among an international panel … Objective To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. Method A Delphi survey was conducted among an international panel of experts on FGR. Panel members were provided with 18 literature-based parameters for defining FGR and were asked to rate the importance of these parameters for the diagnosis of both early and late FGR on a 5-point Likert scale. Parameters were described as solitary parameters (parameters that are sufficient to diagnose FGR, even if all other parameters are normal) and contributory parameters (parameters that require other abnormal parameter(s) to be present for the diagnosis of FGR). Consensus was sought to determine the cut-off values for accepted parameters. Results A total of 106 experts were approached, of whom 56 agreed to participate and entered the first round, and 45 (80%) completed all four rounds. For early FGR (< 32 weeks), three solitary parameters (abdominal circumference (AC) < 3rd centile, estimated fetal weight (EFW) < 3rd centile and absent end-diastolic flow in the umbilical artery (UA)) and four contributory parameters (AC or EFW < 10th centile combined with a pulsatility index (PI) > 95th centile in either the UA or uterine artery) were agreed upon. For late FGR (≥ 32 weeks), two solitary parameters (AC or EFW < 3rd centile) and four contributory parameters (EFW or AC < 10th centile, AC or EFW crossing centiles by > two quartiles on growth charts and cerebroplacental ratio < 5th centile or UA-PI > 95th centile) were defined. Conclusion Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

2017-06-28

Daniel L. Rolnik , D. Wright , Liona C. Poon +7 more

Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.In … Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).

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Hypertensive Disorders of Pregnancy

2018-06-13

Mark Brown , Laura A. Magee , Louise C. Kenny +7 more

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Preeclampsia

2019-03-28

Sarosh Rana , Elizabeth Lemoine , Joey P. Granger +1 more

Hypertensive disorders of pregnancy—chronic hypertension, gestational hypertension, and preeclampsia—are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with … Hypertensive disorders of pregnancy—chronic hypertension, gestational hypertension, and preeclampsia—are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.

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Hypertension in Pregnancy

2013-10-23

James M. Roberts , Phyllis August , George L. Bakris +7 more

Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy Hypertension in Pregnancy was developed by the Task Force on Hypertension in Pregnancy: James M. … Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy Hypertension in Pregnancy was developed by the Task Force on Hypertension in Pregnancy: James M. Roberts, MD, Chair; Phyllis A. August, MD, MPH; George Bakris, MD; John R. Barton, MD; Ira M. Bernstein, MD; Maurice Druzin, MD; Robert R. Gaiser, MD; Joey R Granger, PhD; Arun Jeyabalan, MD, MS; Donna D. Johnson, MD; S. Ananth Karumanchi, MD; Marshall Lindheimer, MD; Michelle Y. Owens, MD, MS; George R. Saade, MD; Baha M. Sibai, MD; Catherine Y. Spong, MD; Eleni Tsigas; and the American College of Obstetricians and Gynecologists' staff: Gerald F. Joseph, MD; Nancy O'Reilly, MHS; Alyssa Politzer; Sarah Son, MPH; and Karina Ngaiza. The information in Hypertension in Pregnancy should not be viewed as a body of rigid rules. The guidelines are general and intended to be adapted to many different situations, taking into account the needs and resources particular to the locality, the institution, or the type of practice. Variations and innovations that improve the quality of patient care are to be encouraged rather than restricted. The purpose of these guidelines will be well served if they provide a firm basis on which local norms may be built.

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy

2000-07-01

Gestational Hypertension and Preeclampsia

2020-05-22

Hypertensive disorders of pregnancy constitute one of the leading causes of maternal and perinatal mortality worldwide. It has been estimated that preeclampsia complicates 2–8% of pregnancies globally (1). In Latin … Hypertensive disorders of pregnancy constitute one of the leading causes of maternal and perinatal mortality worldwide. It has been estimated that preeclampsia complicates 2–8% of pregnancies globally (1). In Latin America and the Caribbean, hypertensive disorders are responsible for almost 26% of maternal deaths, whereas in Africa and Asia they contribute to 9% of deaths. Although maternal mortality is much lower in high-income countries than in developing countries, 16% of maternal deaths can be attributed to hypertensive disorders (1, 2). In the United States, the rate of preeclampsia increased by 25% between 1987 and 2004 (3). Moreover, in comparison with women giving birth in 1980, those giving birth in 2003 were at 6.7-fold increased risk of severe preeclampsia (4). This complication is costly: one study reported that in 2012 in the United States, the estimated cost of preeclampsia within the first 12 months of delivery was $2.18 billion ($1.03 billion for women and $1.15 billion for infants), which was disproportionately borne by premature births (5). This Practice Bulletin will provide guidelines for the diagnosis and management of gestational hypertension and preeclampsia.

Pre-eclampsia

2010-07-03

Eric A.P. Steegers , Peter von Dadelszen , Johannes J. Duvekot +1 more

Pre-eclampsia

2005-02-01

Baha M. Sibai , Gus Dekker , Michael J. Kupferminc

Pre-eclampsia

2015-09-03

Ben W. Mol , Claire T. Roberts , Shakila Thangaratinam +3 more

Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia

2006-10-25

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The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP)

2001-01-01

Mark Brown , Marshall D. Lindheimer , Michael de Swiet +2 more

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Pre-eclampsia

2005-03-04

B. M. Sibai , G.A. Dekker , Michael J. Kupferminc

Practice bulletin #33: diagnosis and management of preeclampsia and eclampsia

2002-01-01

ACOG Committee on Obstetric Practice

Hypertensive disease occurs in approximately 12-22% of pregnancies, and it is directly responsible for 17.6% of maternal deaths in the United States (1,2). However, there is confusion about the terminology … Hypertensive disease occurs in approximately 12-22% of pregnancies, and it is directly responsible for 17.6% of maternal deaths in the United States (1,2). However, there is confusion about the terminology and classification of these disorders. This bulletin will provide guidelines for the diagnosis and management of hypertensive disorders unique to pregnancy (ie, preeclampsia and eclampsia), as well as the various associated complications. Chronic hypertension has been discussed elsewhere (3).

Circulating angiogenic factors and the risk of preeclampsia*

2004-05-01

The following abstracts of articles from leading journals have been selected on the basis of their importance to the practice of obstetrics and gynecology. The following abstracts of articles from leading journals have been selected on the basis of their importance to the practice of obstetrics and gynecology.

Preeclampsia and risk of breast cancer: A longitudinal cohort study of tumor histology

2025-06-25

Shu Qin Wei , Valérie Leduc , Brian J. Potter +6 more | International Journal of Cancer

Abstract Patients with preeclampsia have a reduced risk of breast cancer, but it is not clear if the protective effect extends to all types of breast tumors. Our objective was … Abstract Patients with preeclampsia have a reduced risk of breast cancer, but it is not clear if the protective effect extends to all types of breast tumors. Our objective was to determine the association of preeclampsia with ductal, lobular, and other breast cancer histology. We conducted a longitudinal cohort study of 1,459,716 patients who had pregnancies between 1989 and 2022 in Quebec, Canada. The main exposure measure was preeclampsia. The outcome was breast cancer, including ductal, lobular, and other histological subtypes diagnosed up to 34 years after childbirth. We included in situ, localized invasive, and metastatic breast cancer. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between preeclampsia and breast cancer histology, adjusted for maternal characteristics. Patients with preeclampsia had a lower incidence of breast cancer than patients without preeclampsia (82.1 vs. 111.7 per 100,000 person‐years). Preeclampsia was associated with a 16% lower risk of breast cancer compared with no preeclampsia (HR 0.84, 95% CI 0.79–0.89), including a 14% lower risk of ductal (HR 0.86, 95% CI 0.81–0.93) and 31% lower risk of lobular tumors (HR 0.69, 95% CI 0.55–0.87). The protective association was present for in situ, localized invasive, and metastatic breast tumors. Preeclampsia was not associated with mucinous, medullary, papillary, or other breast cancer histology. We conclude that patients with preeclampsia are less likely to develop ductal and lobular breast cancer than patients with normotensive pregnancies, but do not have a reduced risk of other types of breast cancer.

Diagnostik der Präeklampsie ab dem zweiten Trimester – Bedeutung von sFlt-1 und PlGF

2025-06-25

Julia Franke , Holger Stepan | Die Gynäkologie

Exposure to Fine Particulate Matter (PM2.5) and Heavy Metals During the Second Trimester of Pregnancy Increases the Risk of Preeclampsia and Eclampsia: An Analysis of National Health Insurance Claims Data from South Korea

2025-06-25

Kuen Su Lee , Won Kee Min , Yoon Ji Choi +3 more | Medicina

Background and Objectives: Air pollutants have been shown to affect hypertensive disorders and placental hypoxia due to vasoconstriction, inflammation, and oxidative stress. The objective of this study was to evaluate … Background and Objectives: Air pollutants have been shown to affect hypertensive disorders and placental hypoxia due to vasoconstriction, inflammation, and oxidative stress. The objective of this study was to evaluate whether high levels of maternal exposure to heavy metals during the second trimester of pregnancy are associated with an increased risk of preeclampsia and eclampsia, using national health insurance claim data from South Korea. Methods: Data on mothers and their newborns from 2016 to 2020, provided by the National Health Insurance Service, were used (n = 1,274,671). Exposure data for ambient air pollutants (PM2.5, CO, SO2, NO2, and O3) and heavy metals (Pb, Cd, Cr, Cu, Mn, Fe, Ni, and As) during the second trimester of pregnancy were retrieved from the Korea Environment Corporation. Atmospheric condition data based on the mother’s registration area were matched. A logistic regression model was adjusted for maternal age, infant sex, season of conception, and household income. Results: In total, 16,920 cases of preeclampsia and 592 cases of eclampsia were identified. In the multivariate model, copper exposure remained significantly associated with an increased risk of preeclampsia (odds ratio: 1.011; 95% confidence interval: 1.001–1.023), and higher ozone exposure during pregnancy was associated with an elevated risk of eclampsia. Conclusions: Increased copper exposure during the second trimester of pregnancy was associated with a high incidence of preeclampsia.

Sex Differences in Hypertension Risk: Insights from Placental Genomics and Pregnancy-Driven Vascular Programming

2025-06-24

Efthalia Moustakli , Anastasios Potiris , Athanasios Zikopoulos +7 more | International Journal of Molecular Sciences

The prevalence, pathogenesis, and long-term consequences of hypertension differ significantly across the sexes, and pregnancy is a special physiological stress test that can reveal a woman’s underlying cardiovascular sensitivity. In … The prevalence, pathogenesis, and long-term consequences of hypertension differ significantly across the sexes, and pregnancy is a special physiological stress test that can reveal a woman’s underlying cardiovascular sensitivity. In addition to being direct risks to the health of the mother and fetus, hypertensive disorders of pregnancy (HDPs), especially preeclampsia, are also reliable indicators of future hypertension and cardiovascular disease in those who are afflicted. Fetal sex has a substantial impact on maternal vascular adaptation, according to new data from placental transcriptomics and epigenetics. This may be due to variations in the expression of angiogenic, immunomodulatory, and vasoactive genes. Sex-specific patterns of placental function, inflammation, and endothelium control are specifically influenced by X-linked gene dosage, escape from X-inactivation, and sex chromosomal composition. These biological variations highlight the placenta’s potential function as a mediator and indicator of maternal cardiovascular risk, and they may help to explain why the incidence and severity of hypertensive pregnancy challenges vary depending on the fetal sex. The purpose of this review is to summarize the state of the art regarding how placental genetics and fetal sex influence maternal hypertensive risk both during and after pregnancy. Additionally, it will investigate how these findings may influence sex-specific cardiovascular screening, prediction, and prevention methods.

Investigating the Accuracy of Ultrasound Imaging in Measuring Fetal Weight in Comparison with the Actual Postpartum Weight

2025-06-24

Sultan Abdulwadoud Alshoabi , Abdulhadi M. Tarshun , Ziyad O. Alnoman +7 more | Pediatric Reports

Background: Antenatal ultrasonography measurements of the estimated fetal weight (EFW) are a critical point in the decision-making process of obstetric planning and management to preserve the safety of both the … Background: Antenatal ultrasonography measurements of the estimated fetal weight (EFW) are a critical point in the decision-making process of obstetric planning and management to preserve the safety of both the newborn and the mother. This study aims to investigate the accuracy of ultrasonography to measure the EFW in comparison with the actual birth weight (BW) measured immediately after delivery. Methods: In this retrospective study, electronic records of 270 newborns who fulfilled the inclusion criteria were retrieved. A structured data sheet was used to collect the EFW, calculated by the Hadlock A formula using real-time ultrasound imaging on the day of delivery or the day before, and the actual BW immediately after delivery. Results: Out of 270 fetuses, 53.7% (145) were female, and 46.3% (125) were male. The mean BW was 2918.1 ± 652.81 g (range: 880 to 5100). The mean EFW was 3271.55 ± 691.47 g (range: 951 to 4942). The mean gestational age was 38 ± 2.48 weeks (range: 29 to 42). Spearman’s rho correlation test revealed strong compatibility between EFW and BW (r = 0.82, p < 0.001). Linear regression analysis showed a strong correlation between EFW and BW (R = 0.875, R2 = 0.766, and p < 0.001). The cross-tabulation test showed 86.8%, 78.4%, and 26.9% compatibility between measurements of EFW and the true BW in group-1 (<2500 g), group-2 (2500–4000 g), and group-3 (>4000 g) fetuses (p< 0.001). Conclusions: EFW using ultrasonography yields high compatibility with the actual BW. Despite the slight overestimation, ultrasonography provides high clinical value in obstetric assessment and subsequent management.

Association between Adverse Outcomes and Middle Cerebral Artery Pulsatility Index Change Based on Maternal Position Change

2025-06-24

Itamar Futterman , Rodney A. McLaren , Meghna Ramaswamy +2 more | American Journal of Perinatology

Abstract We have previously demonstrated that maternal position changes directly affect the fetal middle cerebral artery (MCA) Doppler pulsatility indices (PI) and may serve as a predictor for adverse pregnancy … Abstract We have previously demonstrated that maternal position changes directly affect the fetal middle cerebral artery (MCA) Doppler pulsatility indices (PI) and may serve as a predictor for adverse pregnancy outcomes. We sought to confirm whether changes in fetal MCA Doppler PI due to position changes are associated with adverse outcomes. We conducted a prospective cohort study of pregnant people with a singleton, nonanomalous fetus, recruited between 18 and 24 weeks of gestation, in a single tertiary care center from December 2021 to February 2022. MCA Dopplers were obtained, and PI indices were measured and recorded, first in the supine position and then in the maternal left lateral (LL) position. The primary outcome was a composite of adverse outcomes (preeclampsia, fetal growth restriction, and oligohydramnios). Based on our prior findings suggesting that a PI Δ of 0.22 may serve as a dividing threshold between low- high-risk pregnancies, we divided the cohort into those above and below Δ = 0.22. Demographics were compared using univariable analyses. Multivariable logistic regression was performed comparing the composite and individual pregnancy outcomes controlling for statistically significant variables. We recruited 228 patients and followed them to delivery. There were 107 that had a PI Δ < 0.22 and 121 that had a PI Δ ≥0.22. The primary outcome of composite adverse outcomes did not differ between the groups (adjusted odd ratio [aOR]: 0.53; 95% confidence interval [CI]: 0.26–1.08). However, pregnancies with PI Δ ≥0.22 were more likely to develop preeclampsia than pregnancies with PI Δ < 0.22 (aOR: 3.30; 95% CI: 1.02–10.69). The primary outcome of composite adverse outcomes did not differ between the groups. However, we did find that a second trimester fetal MCA PI Δ ≥0.22 with maternal position changes at anatomy ultrasound was associated with developing preeclampsia. This data suggests that there may be an association between early decreased fetoplacental reserve and the development of preeclampsia.

First-trimester screening for preeclampsia between 11 and 13 + 6 weeks of gestation and adverse perinatal outcomes

2025-06-24

Karine Mendonça Davi Rodrigues , M. Silva , Bárbara Elisa Basílio de Oliveira +5 more | Journal of Ultrasound

Acute effect of statins on vascular reactivity in maternal and placental arteries from pregnancies complicated by preeclampsia

2025-06-24

Chinedu Agwu , Jenny Myers , Mark Wareing +1 more | Frontiers in Physiology

Introduction This study aimed to investigate the acute effects of statins on maternal and fetoplacental vascular reactivity in vessels from pregnancies affected by pre-eclampsia (PE), a leading cause of maternal … Introduction This study aimed to investigate the acute effects of statins on maternal and fetoplacental vascular reactivity in vessels from pregnancies affected by pre-eclampsia (PE), a leading cause of maternal and fetal morbidity and mortality. Statins have been proposed as a candidate therapy due to their pleiotropic effects but evidence of statins’ ability to ameliorate the observed endothelial dysfunction in PE is lacking. Methods Human chorionic plate arteries (CPAs) and omental arteries (OAs) from normal and PE pregnancies were mounted on a wire myograph. Contraction was assessed with KPSS and the thromboxane mimetic U46619. Arteries were incubated for 2 h with 1 µM or 10 µM pravastatin, pitavastatin or simvastatin (pitavastatin only in OAs). U46619 dose–response curves were repeated or dose-response curves with NO-donor SNP or endothelium-dependent bradykinin (BK) performed following U46619 pre-constriction. Results CPAs from normal and PE pregnancies showed similar responses following exposure to the vasoconstrictive agent U46619 and the relaxatory agent SNP. Short-term exposure to pravastatin, simvastatin and pitavastatin did not cause detrimental effects on CPA reactivity. Acute exposure of OAs from PE pregnancies to pitavastatin (1 µM) did not reduce U46619-mediated contraction or enhance BK-mediated relaxation of vessels although in this study ex vivo endothelial function of OAs from PE pregnancies was not different to those in normotensive pregnancy pre incubation. Discussion In conclusion, this study did not demonstrate an effect on vascular reactivity of maternal systemic or fetoplacental arteries following acute treatment of statins. Future studies investigating the effect of longer-term statin exposure on maternal and fetoplacental vascular reactivity may help towards treatment strategies for vascular dysfunction in PE-affected patients.

Excessive Iron Induces Macrophage Dysfunction in the Liver, Causing Adverse Pregnancy Outcomes in Mice

2025-06-24

Sayaka Shimazaki , Ren Ozawa , Akari Isobe +3 more | Metabolites

Background: Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating … Background: Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating iron homeostasis and pregnancy conditions. However, the role of macrophages in iron metabolism during pregnancy is unclear. Therefore, we used mouse models to investigate whether maternal iron overload induces pregnancy complications and their interactions with macrophages. Methods and Results: Administration of high-dose iron (iron dextran) by intraperitoneal injection to pregnant mice induced pregnancy complications such as fetal death, but low-dose iron did not affect fetal weight. In the placenta, the amount of iron was significantly increased and levels of macrophages were decreased by iron administration. In the liver, iron administration dramatically increased the amount of iron, with increased inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6. Macrophages were observed to surround deposited iron in the liver. In an in vitro experiment, treatment with iron stimulated TNFα secretion with cell death in macrophages, but not in liver cells. To investigate the importance of macrophages during pregnancy, clodronate liposomes were administered to reduce macrophages in pregnant mice. The macrophage reduction in pregnant mice resulted in an increased absorption rate and fetal growth restriction, together with higher iron accumulation and inflammatory cytokines in the liver. Conclusions: Maternal excess iron may induce inflammatory conditions with macrophage dysfunction in the liver, resulting in pregnancy complications. The reduction in macrophages also induced higher iron levels and adverse effects during pregnancy, suggesting a vicious cycle between excessive iron and macrophage dysfunction during pregnancy.

Role of Fetal Medicine Foundation (FMF) Instrument as a Screening Pre-eclampsia: A Cohort Study

2025-06-24

Murwani Emasrissa Latifah , Nuswil Bernolian , Peby Maulina Lestari +5 more | Journal of Posthumanism

Maternal death is still a problem among pregnant women. One of the most prevalent causes of maternal death is preeclampsia. Preeclampsia contributes not only to maternal death, but also increases … Maternal death is still a problem among pregnant women. One of the most prevalent causes of maternal death is preeclampsia. Preeclampsia contributes not only to maternal death, but also increases fetal morbidity. Early screening for preeclampsia is a key factor to managing the condition. The Fetal Medicine Foundation (FMF) has developed an algorithm to predict preeclampsia during the first trimester of pregnancy. However, there has been lack of studies done in Indonesia its usage. Therefore, this study aims to examine the accuracy of the FMF algorithm as a screening tool to identify preeclampsia in women in the first trimester of pregnancy. //Prospective cohort study done in Obstetrics and Gynecology Department of Mohammad Hoesin Hospital Palembang in January-December 2023. Sixty subjects that met the inclusion criteria were followed from 11 to 13+6 weeks to birth. All subjects undergo history taking for maternal and obstetrics history, physical examination, in particular mean arterial pressure (MAP) measurement, ultrasonography examination to evaluate mean uterine artery pulsatility index (UtA-PI), crown-rump length (CRL), and laboratory testing for pregnancy-associated plasma protein-A [PAPP-A] and placental growth factor [PlGF]. The outcome of this study is the incidence of preeclampsia as well as the detection rate (accuracy rate), false positive rate, positive predictive value (PPV), and negative predictive value (NPV) of the FMF algorithm. Data were analyzed using SPSS version 25.0 with a significance level of p <0.05 and a 95% CI. Kolmogorov Smirnov test was used for data homogeneity, Chi-square or Fisher test for categorical data, One way anova and Kruskal wallis test for numerical data. Sixty subjects were enrolled. Among these, 30 subjects subsequently developed preeclampsia, with 18 (30%) experiencing early-onset preeclampsia, 12 (20%) experiencing late-onset preeclampsia, and 30 (50%) not developing preeclampsia (normotension). There was no significant difference in maternal characteristics and obstetric history among the three groups. MAP is found to be significantly different, with the highest found in the early onset preeclampsia group (p=0.021). Uterine artery pulsatility index (UtA-PI) was significantly higher in early-onset and late-onset preeclampsia subjects (p=0.019). There was no significant difference among the three groups in CRL. Serum PIGF was significantly lower in early onset and late-onset preeclampsia subjects (p-0.0001). Serum PAPP-A is also significantly lower in the early-onset preeclampsia subjects (p=0.0002). The combination of FMF/MAP, UtA-PI, yields the highest accuracy in predicting preeclampsia with 100% values for sensitivity, specificity, PPV, and NPV (p=0,000). The other combinations show lower accuracy, but quite good values of specificity and sensitivity. The FMF algorithm is an accurate screening tool to identify preeclampsia in the first trimester of pregnancy.

Could Low Serum Albumin Level Be an Independent Marker of Severe Preeclampsia?

2025-06-24

Elena Ciciu , Aurelia Alexandru , Bogdan Cimpineanu +5 more | Healthcare

Background: Preeclampsia (PE) remains a significant cause of maternal and fetal morbidity and mortality, with diagnostic criteria still evolving. Serum albumin, a potential marker of endothelial dysfunction and protein loss, … Background: Preeclampsia (PE) remains a significant cause of maternal and fetal morbidity and mortality, with diagnostic criteria still evolving. Serum albumin, a potential marker of endothelial dysfunction and protein loss, has been proposed as a severity indicator in PE. This study evaluates the clinical utility of serum albumin levels, particularly values below 2 g/dL, in assessing PE severity and predicting maternal–fetal complications. Methods: We conducted a prospective and descriptive study including 59 pregnant women diagnosed with PE. The participants were divided into mild (n = 23) and severe (n = 36) PE groups based on national guidelines. Serum albumin, 24 h proteinuria, renal and hepatic function markers, and fetal outcomes were analyzed. ROC curve analysis was employed to determine albumin’s diagnostic performance. Results: Serum albumin levels were significantly lower in the severe PE group compared to the mild PE group (1.82 ± 0.50 vs. 2.44 ± 0.36 g/dL, p < 0.001). ROC analysis identified a threshold of 2.3 g/dL (sensitivity: 88.9%, specificity: 73.9%) for distinguishing PE severity. A strong association was observed between albumin < 2 g/dL and severe proteinuria (>3 g/24 h), but no significant association emerged with renal or hepatic dysfunction, fetal complications, or birth outcomes. Conclusions: Although serum albumin < 2 g/dL is associated with severe proteinuria, it does not independently correlate with other maternal or fetal complications in PE. These findings suggest that albumin may serve as a complementary, but not a standalone, marker in assessing PE severity.

A steep-increasing blood pressure trajectory from early pregnancy is associated with birth outcomes in the EDEN mother-child cohort

2025-06-23

Briana DeStaffan , Muriel Tafflet , Grégory Lailler +6 more | Journal of Hypertension

Background: An enhanced consideration of blood pressure (BP) dynamics during pregnancy could improve its monitoring. Distinct BP trajectories may exist, and some have been linked to adverse fetal development. Using … Background: An enhanced consideration of blood pressure (BP) dynamics during pregnancy could improve its monitoring. Distinct BP trajectories may exist, and some have been linked to adverse fetal development. Using maternal BP measurements spanning almost the entire pregnancy, this study aimed to identify trajectories and assess their association with birth outcomes. Methods: Routine BP measurements (median = 8) were extracted from the obstetric records of 1849 mothers from the French EDEN birth cohort. Outcomes included birth weight z-score, prematurity and, for a subsample ( n = 1377), placental weight and birth weight-to-placental weight ratio. Maternal SBP trajectories were identified by Latent Class Growth Mixture Modeling. Associations with outcomes were analyzed using adjusted linear or logistic regressions. Results: Two BP trajectories were identified: a first U-shaped and a second steep-increasing, comprising 96 and 4% of mothers, respectively. The steep-increasing trajectory reached the hypertensive threshold around 30 weeks of gestation. Over half of mothers in this trajectory had a hypertensive disorder diagnosis, and 24% had preeclampsia. Mothers in this trajectory had newborns with lower birth weight z-scores [β = -0.31, 95% confidence interval (95% CI) = -0.55 to -0.07] and/or increased likelihood of premature delivery (odds ratio = 4.02, 95% CI = 2.04–7.50). No associations were observed with placental outcomes. Conclusion: Our results suggest the existence of a steep-increasing BP trajectory from the first weeks of pregnancy and associated with poorer birth outcomes. Further investigation into this trajectory's determinants could lead to improved hypertensive disorder risk stratification, ultimately aiding in the prevention of related maternal and fetal consequences.

Urinary Nephrin Concentrations in Preeclampsia (with and without Complications) vs Normal Pregnancies

2025-06-23

Anastasia M. Lumentut , Adhi Pribadi , Amillia Siddiq +4 more | Medical Science Monitor

Construct a nomogram prediction and evaluation of influencing factors of adverse pregnancy outcomes in GDM patients based on plasma miR-144-3p levels

2025-06-23

Sanqiang Niu , Pengwen Wu , Yiran Li +3 more | Frontiers in Endocrinology

Objective To examine the expression levels of miR-144-3p in the plasma of patients with gestational diabetes mellitus (GDM) and to construct a nomogram for predicting and evaluating factors influencing adverse … Objective To examine the expression levels of miR-144-3p in the plasma of patients with gestational diabetes mellitus (GDM) and to construct a nomogram for predicting and evaluating factors influencing adverse pregnancy outcomes (APO) in GDM based on plasma miR-144-3p levels. Methods This study included 442 pregnant women, comprising 216 diagnosed with GDM (GDM group) and 226 with normal glucose tolerance (NGT group). Plasma miR-144-3p levels in both groups were measured using reverse transcription real-time polymerase chain reaction (RT-qPCR). The diagnostic performance of plasma miR-144-3p for GDM was assessed by receiver operating characteristic (ROC) curve analysis. During pregnancy, the GDM group was followed, and outcomes were categorized into two groups: 132 with favorable pregnancy outcomes (FPO) and 84 with APO. A random number table method was applied to divide the GDM group into a training set (n=151) and a validation set (n=65) using a 7:3 ratio. Differences in variables across pregnancy outcome subgroups in the training set were examined. Univariate and multivariate logistic regression analyses were performed to identify risk factors for APO in GDM. Based on these factors, a nomogram prediction model was developed to estimate the risk of APO in GDM. The model’s performance was evaluated using area under the curve (AUC) analysis, calibration curve analysis, and decision curve analysis (DCA). Results The expression of miR-144-3p was significantly higher in the GDM group than in the NGT group ( p &lt; 0.05). miR-144-3p showed an AUC of 0.877, with a sensitivity of 81.09% and a specificity of 91.20% for diagnosing GDM. No statistically significant differences were observed in general clinical characteristics between the training and validation sets. In the training set, gestational weight gain (GWG), the number of OGTT abnormalities, glycaemic control (GC), and miR-144-3p expression varied significantly between the APO and FPO subgroups ( p &lt; 0.05). Multivariate logistic regression analysis identified increased GWG, the number of OGTT abnormalities, poor GC, and higher miR-144-3p levels as independent risk factors for APO in GDM. The AUC of the nomogram based on these variables was 0.881 in the training set and 0.855 in the validation set. Calibration curves indicated good agreement between predicted and actual outcomes in both sets. The DCA showed a clear net clinical benefit and stable predictive utility. Conclusion Elevated plasma miR-144-3p levels in pregnant women with GDM may contribute to the occurrence of APO. The number of OGTT abnormalities and glycaemic control were also identified as independent risk factors. A nomogram incorporating miR-144-3p and these clinical indicators displays strong predictive accuracy and provides a practical tool for assessing APO risk in GDM.

Detection rate of the Japan society of obstetrics and gynecology’s definition of fetal growth restriction for predicting small-for-gestational-age neonates

2025-06-23

Tetsu Wakimoto , Saki Kunimoto , Ryo Yamamoto +2 more | Journal of Medical Ultrasonics

Gestational hypertension: fetal and placental characterization using MRI and ultrasound

2025-06-23

Junqin Zhang , Xue Tang , Zhongxiang Ding +1 more | The Journal of Maternal-Fetal & Neonatal Medicine

This study aims to integrate MRI and ultrasound (US) assessments of fetal and placental growth and development in cases of gestational hypertension (GH), evaluating their potential utility for clinical management … This study aims to integrate MRI and ultrasound (US) assessments of fetal and placental growth and development in cases of gestational hypertension (GH), evaluating their potential utility for clinical management and prognostic evaluation. A retrospective study analyzed 84 pregnant women (39 with GH, 45 controls) to compare fetal and placental parameters using MRI and US. Parameters included placental thickness (PT), relative signal intensity(rSI), relative apparent diffusion coefficient(rADC), lung-to-liver signal intensity ratio(LLSIR), and various indices of the umbilical and middle cerebral arteries. Differences between the GH and control groups were statistically examined. Binary logistic regression identified independent risk factors for GH-related adverse outcomes, leading to the creation of predictive models (MRI-only, US-only, and MRI+US). ROC curves assessed each model's predictive performance, and the DeLong test compared the area under the curve (AUC) among models. In comparison to the control group, the GH group showed: 1) Increased PT thickness and decreased rSI and rADC values (p < 0.05). 2) Higher vascular resistance, as indicated by significantly elevated systolic-diastolic ratio (UA-S/D ratio), pulsatility index (UA-PI), and resistance index (UA-RI) of the umbilical artery (all p < 0.05), was observed. 3) Shorter biparietal diameter (BPD, p < 0.05) and reduced LLSIR (p < 0.001). 4) UA-PI, UA-S/D, PT, rADC, and rSI were identified as independent risk factors for GH through binary logistic regression. ROC analysis demonstrated that the MRI+US model (AUC = 0.89, sensitivity = 85%, specificity = 93%) significantly improved the prediction accuracy, with the combined model's AUC value being significantly different from other models (p < 0.05). The integration of MRI and US offers a robust evaluation of placental and fetal growth and development in GH patients. Furthermore, the combined utilization of MRI and US techniques exhibits enhanced accuracy in predicting adverse pregnancy outcomes.

Long-term follow-up of a neonatal cohort after intrauterine exposure to maternal heparin-mediated extracorporal LDL-precipitation (HELP)-apheresis in very preterm preeclampsia

2025-06-23

Martin Kuntz , Cornelia Lorey , Christine Contini +4 more | Pregnancy Hypertension

Preterm preeclampsia represents a significant contributor to maternal and fetal/neonatal morbidity and frequently results in preterm delivery. The Freiburg preeclampsia HELP (heparin-mediated extracorporal LDL-precipitation)-Apheresis study was a pilot study designed … Preterm preeclampsia represents a significant contributor to maternal and fetal/neonatal morbidity and frequently results in preterm delivery. The Freiburg preeclampsia HELP (heparin-mediated extracorporal LDL-precipitation)-Apheresis study was a pilot study designed to investigate the effects of HELP-apheresis on the clinical and laboratory outcome of severe preeclampsia. Results of the study were promising, indicating that this approach may be beneficial in prolonging pregnancy. Nevertheless, the long-term effects on the children were not determined yet. Long-term outcomes of the 12 children from the Freiburg preeclampsia HELP-Apheresis study (6 from the intervention group, 6 from the control cohort) were assessed using Bayley Scales at 24 months corrected age and a parent questionnaire (CBCL4-18) at approximately 10 years of age. Children exposed to maternal HELP-apheresis demonstrated a generally favorable outcome in terms of Bayley Scales, school and social skills, as well as body growth at 10 years of age. No significant difference between the intervention and the control cohort was observed. The results were consistent with larger cohorts studying the long-term outcomes of very low birth weight infants. Prenatal exposure to maternal HELP-apheresis did not have any negative effect on the long-term outcome of very preterm infants born to mothers with severe preeclampsia. However, a potential beneficial impact of the intervention due to the prolongation of pregnancy would have been too small to be discernible. The results of this study justify further investigation of lipid-apheresis as a possible treatment option in severe, very preterm preeclampsia.

Prevalence and outcomes of pregnancy-induced hypertension among women seeking maternity services in selected tertiary hospitals of Gandaki Province

2025-06-23

Bandi Gurung , Rekha Thapaliya , Rajesh Adhikari | Journal of Gandaki Medical College-Nepal

Introduction: Pregnancy-induced hypertension (PIH), particularly pre-eclampsia and eclampsia, significantly contributes to maternal and perinatal mortality globally. This study aimed to assess the prevalence and outcomes of PIH among women seeking … Introduction: Pregnancy-induced hypertension (PIH), particularly pre-eclampsia and eclampsia, significantly contributes to maternal and perinatal mortality globally. This study aimed to assess the prevalence and outcomes of PIH among women seeking maternity services in tertiary hospitals in Gandaki Province. Methods: A retrospective research design was adopted, using a census method. The secondary data of women seeking maternity services in selected tertiary hospitals of Gandaki Province between Shrawan 2079 to Ashad 2080 was included in the study. Medical records and logbooks were reviewed, focusing on 751 women diagnosed with PIH. Data were analyzed using descriptive statistics. Results: Out of 11,927 women, 751 women seeking maternity services in Gandaki province had PIH. More than half (53.4%) had gestational hypertension, 35% had pre-eclampsia, 6.5% had eclampsia, and 5.1% had chronic hypertension with superimposed pre-eclampsia. Regarding maternal outcomes, 11.5% had pre-labour rupture of membrane, 1.3% had postpartum hemorrhage, 0.9% had abruptio placenta, and 0.3% had acute respiratory distress syndrome. Likewise, 18.5% had fetal distress, 13.6% had oligohydramnios, 8% had intrauterine growth retardation and 3.1% was intrauterine fetal death or still death. Twenty-five percent had prematurity, 31.4% had low birth weight, and 19.6% were admitted to the newborn intensive care unit. In the study, 0.1% of maternal deaths and 1.6% of neonatal deaths were found in women with PIH. Conclusions: The prevalence of PIH was nearly one-tenth among women seeking maternity services, affecting both maternal and fetal outcomes. Gestational hypertension was the most common type. Implementing awareness programs focused on early diagnosis and treatment of PIH is recommended for better outcomes.

Fetal Thigh Circumference Nomograms Across Gestational Ages: A Retrospective Study

2025-06-22

Ferdinando Antonio Gulino , Giorgio Arcarese , Giosuè Giordano Incognito +7 more | Journal of Personalized Medicine

Background/Objectives: Fetal thigh circumference (ThC) may be a valuable parameter for assessing fetal growth. Thus, this study aimed to establish reference ranges for ThC across gestational ages (GA). Methods: This … Background/Objectives: Fetal thigh circumference (ThC) may be a valuable parameter for assessing fetal growth. Thus, this study aimed to establish reference ranges for ThC across gestational ages (GA). Methods: This retrospective study included singleton pregnancies between 12 and 38 weeks of gestation. ThC measurements were obtained during routine ultrasound examinations. GA was confirmed through the last menstrual period and first-trimester crown–rump length measurements. Percentile ranges for ThC were calculated for each gestational week, and statistical analyses evaluated the relationship between ThC and GA. Results: 48,841 singleton pregnancies were included. A positive correlation was observed between ThC and GA, with ThC values increasing progressively from 12 to 38 weeks. The study established the 10th, 50th, and 90th percentile ranges for ThC, providing reference values for clinical assessments. Conclusions: This study provides reference ranges for fetal ThC across a wide GA range, highlighting its potential as a tool in prenatal care. ThC may offer an additional parameter for monitoring fetal growth, especially when standard measurements are challenging. Further research should investigate the integration of ThC with other fetal growth parameters to enhance its clinical utility. Additionally, these nomograms can be used to assess their usefulness in certain conditions, such as intrauterine growth restriction (IUGR), macrosomia, and congenital skeletal dysplasias.

Ophthalmic Artery Doppler at 11–13 Weeks’ Gestation and Birth of Small-for-Gestational-Age Neonates

2025-06-21

Nicoleta Gana , Dragana Ianosev , Nima Allafi +2 more | Journal of Clinical Medicine

Background/Objective: Small-for-gestational-age (SGA) status constitutes a significant risk factor for adverse neonatal outcomes and predisposes individuals to long-term health complications. Detecting pregnancies at risk early in gestation could significantly improve … Background/Objective: Small-for-gestational-age (SGA) status constitutes a significant risk factor for adverse neonatal outcomes and predisposes individuals to long-term health complications. Detecting pregnancies at risk early in gestation could significantly improve perinatal outcomes. Recent evidence suggests that ophthalmic artery Doppler assessment in the first trimester may contribute to the prediction of impaired placentation reflected in increased risk for preeclampsia. This study aimed to investigate the association between first-trimester ophthalmic artery Doppler parameters and the subsequent birth of small-for-gestational-age (SGA) neonates. Methods: In this prospective observational analysis, 4054 pregnant women underwent ophthalmic artery Doppler evaluation at 11–13 weeks gestation. Maternal demographics, biophysical and biochemical markers, and ophthalmic artery Doppler measurements of pulsatility index (PI) and peak systolic velocity (PSV) ratio were obtained. Outcomes were classified based on birthweight into the ≤3rd percentile and >3rd percentile and ≤10th percentile and >10th percentile groups. To determine the predictive value of Doppler indices, statistical methods included comparative analyses and the receiver operating characteristic (ROC) curves. Results: The analysis indicated that increased PSV ratio at 11–13 weeks gestation correlated with an increased risk of SGA. The PI was not found to be a significant discriminator between pregnancies complicated by SGA and non-SGA pregnancies. Conclusions: First-trimester ophthalmic artery Doppler assessment offers promise as a non-invasive technique for the early identification of pregnancies at risk for SGA neonates. Further validation through large, multicenter studies is needed to confirm its utility and to standardize its use in clinical protocols.

Ultrasound placental image texture analysis using artificial intelligence and deep learning models to predict hypertension in pregnancy

2025-06-21

Urvashi Arora , Palani Vigneshwar , Munagala Krishna Sai +3 more | International Journal of Gynecology & Obstetrics

In the era of whole transcriptome sequencing: Reflections on the Molecular Genetic Effect of Prenatal Sildenafil for Fetal Growth Restriction

2025-06-21

Carsten Bakhuis , Marcel A. G. van der Heyden | Journal of Trial and Error

In this reflection article, we evaluate a sub study of the STRIDER trial by Terstappen et al., which investigated the molecular effects of prenatal sildenafil administration in pregnancies complicated by … In this reflection article, we evaluate a sub study of the STRIDER trial by Terstappen et al., which investigated the molecular effects of prenatal sildenafil administration in pregnancies complicated by fetal growth restriction (FGR). Unfortunately, this trial revealed no clinical benefit and even an increased risk of persistent pulmonary hypertension in neonates. After an early trial cessation, this sub study tried to elucidate tissue-specific sildenafil effects by performing RNA sequencing on placental tissues and human umbilical vein endothelial cells. While no significant differences were found on gene level, modest pathway-level alterations (specifically in nitric oxide and immune signaling pathways) were observed. We here reflect on the methodological strengths of combining clinical and molecular data, but also point out limitations of this study such as the restricted gene set choice and the absence of an analysis stratified by neonatal outcome. For future drug repurposing studies, we highlight the importance of a broad molecular characterization of target tissues to fully explain effects that are observed in clinical trials.

Antepartum Serum Lactate Dehydrogenase and Adverse Obstetric Outcomes in Preeclampsia: A Systematic Review of Prognostic Evidence From Low- and Middle-Income Countries

2025-06-21

Khoa D. Nguyen , Anh TN Khuc , Vanessa Tran +3 more | Cureus

This systematic review evaluated the association between antepartum serum lactate dehydrogenase (LDH) levels and adverse maternal and perinatal outcomes in preeclamptic pregnancies in low- and middle-income countries (LMICs). A comprehensive … This systematic review evaluated the association between antepartum serum lactate dehydrogenase (LDH) levels and adverse maternal and perinatal outcomes in preeclamptic pregnancies in low- and middle-income countries (LMICs). A comprehensive search of PubMed, Embase, and Scopus identified 19 observational studies published between 2000 and 2025, comprising 5,039 pregnant women, including 3,782 preeclampsia diagnoses. Most studies were conducted in South Asia and the Middle East. Although LDH thresholds varied, a consistent trend was observed: higher LDH levels were associated with increased risk of maternal complications such as HELLP syndrome, disseminated intravascular coagulation, acute renal failure, and ICU admission. Perinatal complications, including stillbirth, intrauterine growth restriction, low Apgar scores, and neonatal intensive care unit (NICU) admission, were also more common at LDH levels >800 IU/L. For example, stillbirth occurred in up to 77.7% of cases in the highest LDH group compared to <3% in the lowest. Due to heterogeneity in cut-offs and outcome definitions, meta-analysis was not performed. Overall, elevated antepartum serum LDH appears to be a strong prognostic marker for severe outcomes in preeclamptic pregnancies and may aid clinical triage in LMICs. Further prospective studies are needed to establish standardized thresholds and validate their predictive utility.

Prevalence and Risk Factors of Preeclampsia in Pregnant Women With Gestational Diabetes Mellitus

2025-06-20

Yufeng Ye , Liuyan Zhang , Yonggui Han +1 more | British Journal of Hospital Medicine

Aims/Background Pregnant women with gestational diabetes mellitus (GDM) are at an increased risk of developing preeclampsia, a condition that not only threatens maternal and fetal safety but also compromises organ … Aims/Background Pregnant women with gestational diabetes mellitus (GDM) are at an increased risk of developing preeclampsia, a condition that not only threatens maternal and fetal safety but also compromises organ function. This study aimed to determine the prevalence of preeclampsia among pregnant women with GDM in China and to identify its associated risk factors. Methods A total of 212 GDM patients who underwent prenatal care and delivery at Beilun District People's Hospital between September 2020 and September 2024 were included in the study. Participants were divided into a preeclampsia group (PE group) and a non-preeclampsia group (Non-PE group) based on the presence or absence of preeclampsia. Clinical and demographic data were extracted from the medical record system and compared between the two groups. Univariate and multivariate analyses were conducted to identify factors influencing the occurrence of preeclampsia. Receiver operating characteristics (ROC) curves were used to evaluate the predictive efficacy of statistically different indicators. Results Among the 212 GDM patients, 60 developed preeclampsia (PE group), while 152 did not (Non-PE group), resulting in a preeclampsia prevalence of 28.30% (60/212). Multivariate logistic regression analysis identified high systolic blood pressure (SBP) (p < 0.001), high diastolic blood pressure (DBP) (p = 0.002), elevated body mass index (BMI) (p < 0.001), increased glycated hemoglobin (HbA1c) (p = 0.007), and high blood urea nitrogen (BUN) (p = 0.017) as independent risk factors for preeclampsia in GDM patients. The predictive value for preeclampsia was assessed using ROC curve analysis. When BMI was ≥23.205 kg/m 2 , the area under the curve (AUC) was 0.695 [p < 0.001, 95% CI (0.612, 0.778)], with a sensitivity of 0.683 and specificity of 0.632. For HbA1c ≥5.550%, the AUC was 0.665 [p < 0.001, 95% CI (0.583, 0.747)], with a sensitivity of 0.617 and specificity of 0.658. When BUN was ≥4.250 mmol/L, the AUC was 0.692 [p < 0.001, 95% CI (0.612, 0.772)], with a sensitivity of 0.550 and specificity of 0.763; The combined prediction model of these three parameters yielded an AUC of 0.826 [p < 0.001, 95% CI (0.759, 0.892)], with a sensitivity of 0.783 and specificity of 0.803. Conclusion The prevalence of preeclampsia was significantly higher among patients with GDM. In addition to blood pressure, BMI, HbA1c, and BUN levels are key factors associated with preeclampsia risk and may be used together to assist in predicting GDM patients with preeclampsia. It is necessary to pay more attention to the high-risk groups of preeclampsia and formulate targeted health management strategies to reduce the risk of preeclampsia and improve maternal and neonatal outcomes.

The Fetal Region-specific Optimized Growth Standard (FROGS)—A fetal and birthweight centile calculator validated in a national population

2025-06-20

Natasha Pritchard , Stephen Tong , Teresa M. MacDonald +7 more | PLoS Medicine

Background There is no universally agreed upon obstetric growth standard for use during pregnancy. We aimed to design a simple novel growth standard, which incorporates key beneficial features identified in … Background There is no universally agreed upon obstetric growth standard for use during pregnancy. We aimed to design a simple novel growth standard, which incorporates key beneficial features identified in prior research. Methods and findings We developed the Fetal Region-specific Optimized Growth Standard (FROGS), then validated it following International Federation of Gynaecology and Obstetrics (FIGO) guidelines. FROGS follows the shape of the fetal (ultrasound-based) Hadlock curve. It is region-specific ; allowing adjustment for the mean birthweight and standard deviation of babies born at term in the local population where it will be applied. It provides an exact centile for each gestational day (rather than rounding off by weeks) and is optionally adjustable for fetal sex. Further, FROGS provides an ‘estimate range’ for the estimated fetal weight centile, assuming a 10% ultrasound measurement error. Following development, we validated FROGS in a retrospective cohort study by comparing its ability to identify small babies with an increased risk of adverse perinatal outcomes to four charts in current use: (1) population birthweight chart (Australian Institute of Health and Welfare, AIHW chart); (2) Hadlock’s 1991 fetal chart; (3) Mikolajczyk’s global fetal and birthweight centile chart; and (4) INTERGROWTH-21st fetal growth standards. To do this, we identified infants classified as small for gestational age (<10th centile) by each chart. We then identified non-overlapping <10th centile populations, i.e., infants classified as small by one chart, but not another. We compared rates of stillbirth and adverse perinatal outcomes between the non-overlapping populations. All charts except INTERGROWTH classified similar proportions of infants as <10th centile (10.4% FROGS, 9.3% AIHW, 11.1% Hadlock, 10.9% global, 4.4% INTERGROWTH). Of the three charts that classified similar proportions as <10th centile, infants classified by FROGS were at the highest risk of adverse perinatal outcomes. The infants classified as <10th centile by only FROGS had significantly increased relative risk (RR) of stillbirth, compared to the infants classified as <10th centile by only AIHW (RR 13.1, 95% CI 6.5–26.5), only Hadlock (RR 2.1, 95% CI 1.28–3.56) or only the global chart (RR 1.54, 95% CI 1.00–2.37). The FROGS chart outperformed these three charts in identifying infants at risk of other adverse perinatal outcomes associated with being small for gestational age, such as neonatal intensive care admission, Apgar scores <7 at 5 min, and operative (instrumental) vaginal birth for suspected fetal compromise. The cohort of infants classified as small for gestational age by INTERGROWTH was, in size and risk, closer to the cohort classified as <3rd centile by FROGS (3.4% of infants <3rd). This study is limited in that it retrospectively assesses birthweight, which may have different implications to a prospective evaluation of estimated fetal weight. Conclusions Compared to currently used charts, the Fetal Region-specific Optimized Growth Standard outperforms existing charts that classify a similar proportion of infants as small for gestational age in identifying small infants at increased risk of stillbirth and other serious perinatal outcomes. The FROGS centile algorithm is simple and transparent. It has the potential to be adapted to other local populations, or applied to clinical and research settings globally.

Prevalence of Medical Disorders During Pregnancy in India: A Comprehensive Observational Study to Assess the Prevalence of Hypertension, Diabetes, and Thyroid Disorders During Pregnancy in Indian Women

2025-06-20

J. Revathi , Meena TS , M Pavithra | Cureus

Assessing the impact of maternal blood pressure during pregnancy on perinatal health: A wide-angled Mendelian randomization study

2025-06-20

Fernanda Morales Berstein , Ana Luiza G. Soares , Qian Yang +7 more | medRxiv (Cold Spring Harbor Laboratory)

Background: Observational studies link high blood pressure in pregnancy to numerous adverse pregnancy and perinatal outcomes; however, findings may be affected by residual confounding or reverse causation. This study aimed … Background: Observational studies link high blood pressure in pregnancy to numerous adverse pregnancy and perinatal outcomes; however, findings may be affected by residual confounding or reverse causation. This study aimed to assess the causal effect of blood pressure during pregnancy on a range of pregnancy and perinatal outcomes. Methods: We performed two sample Mendelian randomisation (MR) to assess the effect of systolic and diastolic blood pressure (SBP/DBP) during pregnancy on 16 primary and eight secondary adverse pregnancy and perinatal outcomes. We obtained genetic association data from large-scale metanalyses of genome-wide association studies involving predominantly European ancestry individuals for SBP/DBP (N=1,028,980), and pregnancy and perinatal outcomes (N=77,285-934,566). We used inverse-variance weighted (IVW) MR for main analyses and MR-Egger, weighted median, weighted mode, multivariable MR, and IVW adjusted for fetal genetic effects for sensitivity analyses. Results: A 10 mmHg higher genetically predicted maternal SBP increased the odds of gestational diabetes, induction of labour, low birth weight (LBW), small-for-gestational age, preterm birth (PTB), and neonatal intensive care unit (NICU) admission [OR ranging from 1.09 (95% CI: 1.04 to 1.14) for PTB to 1.33 (1.26 to 1.41) for LBW]; while decreasing the odds of high birth weight (HBW), large-for-gestational age, and post-term birth [OR ranging from 0.76 (0.69 to 0.83) for HBW to 0.94 (0.90 to 0.99) for post-term birth]. We did not find evidence that genetically predicted higher maternal SBP was related to miscarriage or stillbirth. Results for maternal DBP were similar to results for SBP. Overall, the main results were consistent across sensitivity analyses accounting for pleiotropic instruments and fetal genetic effects. Conclusions: Higher maternal blood pressure reduces gestation duration and fetal growth, and increases the risks of induction of labour, gestational diabetes and NICU admission. This and other emerging evidence highlight the value of interventions to control maternal blood pressure during pregnancy to reduce the burden of adverse pregnancy outcomes.

IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway

2025-06-20

Shu Meng , Yanping Qin , Chenyi Lyu +1 more | Current Issues in Molecular Biology

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) … Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients.

Hypertensive Disorders of Pregnancy Deaths: A Four-Year Review at a Tertiary/Quaternary Academic Hospital

2025-06-20

Zahid Khan , Gaynor M. Balie , Lawrence Chauke | International Journal of Environmental Research and Public Health

Background: Hypertensive disorders of pregnancy (HDPs) are a major cause of maternal morbidity and mortality worldwide. Very little progress has been made in reducing HDP-related maternal deaths in low- and … Background: Hypertensive disorders of pregnancy (HDPs) are a major cause of maternal morbidity and mortality worldwide. Very little progress has been made in reducing HDP-related maternal deaths in low- and middle-income countries (LMICs), including South Africa, over the past decade. Aim: The aim of this study was to describe maternal deaths arising from HDPs at tertiary/quaternary hospital in Johannesburg, South Africa, with specific focus on maternal characteristics, management, timing of death, causes, and avoidable factors and to use the information to inform clinical practice. Methods: We conducted a retrospective review of patient clinical records covering the period 1 January 2015 to 31 December 2018. Data on maternal demographic and pregnancy characteristics, management, causes, and timing of death were extracted from the clinical records and transferred into a Microsoft Excel® Spreadsheet and analysed using descriptive statistics. Results: During the study period, 70 maternal deaths were recorded, of which 23 (32.8%) were due to HDP-related complications. The majority of the maternal deaths, 20 (86.9%), occurred during the postpartum period, predominantly affecting Black African women, 23 (100%), with a median age of 27 years. Notably, 18 (78.2%) of the deceased had booked early and attended antenatal care (ANC). Eclampsia emerged as the most common final cause of death. Key avoidable factors included non-adherence to established protocols, particularly failure to initiate aspirin prophylaxis in at-risk women, as well as incorrect or inadequate administration of antihypertensive therapy and magnesium sulphate (MgSO4) prophylaxis. Conclusions: HDP-related maternal deaths are largely preventable. They primarily result from poor quality of care due to a lack of adherence to evidence-based protocol.

Experiences of conducting effective Patient and Public Involvement and Engagement (PPIE) by the WILL Trial (When to Induce Labour to Limit risk in pregnancy hypertension) Management Team

2025-06-20

Katie Kirkham , Sue Tohill , Julie Wade +5 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background</bold>: Patient and Public Involvement and Engagement (PPIE) is an essential element of any clinical trial, to ensure that the research design and resources are acceptable and the trial … <title>Abstract</title> <bold>Background</bold>: Patient and Public Involvement and Engagement (PPIE) is an essential element of any clinical trial, to ensure that the research design and resources are acceptable and the trial produces findings that are relevant to research participants and service-users. The WILL (When to Induce Labour to Limit risk in pregnancy hypertension) Trial Management Team involved a group of patient and public members to develop an infographic, for service-users and -providers, to communicate the risks of chronic and gestational hypertension at term gestational age. <bold>Methods</bold>: Based on national resources for PPIE, including those from the National Institute for Health and Care Research (NIHR) and Health Research Authority, active trial sites were approached to invite women with pregnancy hypertension to the PPIE group, and advertisements were placed on the Action on Pre-Eclampsia Charity (APEC) and NIHR People in Research websites. PPIE resources were established by the Trial Management Team and virtual meetings with the PPIE members held to co-design and develop the infographic from existing trial materials, using Microsoft Publisher. <bold>Results</bold>: Seven diverse PPIE members were involved, six from NIHR People in Research and one from APEC. No members were engaged from active sites. From initial set-up to REC approval of the infographic took nine months, and a considerable time commitment from the Trial Manager and Senior Research Midwives, to navigate practicalities (e.g., team consensus-building). Four meetings were held and 15 iterations of the infographic were developed with the group. The infographic incorporated requests from PPIE members for a design that was inclusive of all races, cultures, abilities, and genders. Discussions with PPIE group members improved our understanding of the acceptability of the trial intervention to some cultures. The Research Ethics Committee (REC) requested revisions to PPIE-approved wording about the risk of stillbirth, from “1 in 1000” to “small increased risk” prior to issuing approval for use. <bold>Conclusions</bold>: More practical support would be useful for researchers seeking to establish PPIE groups, and RECs reviewing resources that are co-produced. Based on our experiences, we offer a summary checklist as an additional resource for PPIE. <bold>Trial registration</bold>: ISRCTN77258279, registered on 05 December 2018.

Pregnancy Outcome in Pregnant Women with Idiopathic Polyhydramnios

2025-06-20

Khalidah Mohammed Amin | Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 )

Background: Polyhydramnios is an excess of the amniotic fluid documented by quantitative ultrasonography. Over 40% of polyhydramnios are prenatally idiopathic and diagnosed with a particular abnormality postnatally; the majority of … Background: Polyhydramnios is an excess of the amniotic fluid documented by quantitative ultrasonography. Over 40% of polyhydramnios are prenatally idiopathic and diagnosed with a particular abnormality postnatally; the majority of other cases remain unexplained. Objective: To compare the maternal and neonatal outcomes of pregnancies with idiopathic polyhydramnios to pregnancies without polyhydramnios. Methods: A retrospective case-control study involving 38 singleton pregnancies as cases and 65 as controls, outcomes concerning preterm delivery, mode of delivery, presence or absence of antepartum and postpartum hemorrhage, birth weight, weight for gestational age, Apgar score, fetal distress, neonatal intensive care unit (NICU) admission, stillbirth, and neonatal death were then compared. Results: Cases showed a significantly higher preterm delivery rate (52.6% vs. 9.2%), cesarean section prevalence (76.3% vs. 23.1%), and maternal postpartum hemorrhage (PPH) (21.1% vs. 6.2%) compared to controls. Neonates from cases had significantly lower 1-minute (6.3 vs. 7.9) and 5-minute Apgar scores (8.0 vs. 9.0), more significant birth weight variability (3100 vs. 3240g), and higher rates of newborns large for gestational age (LGA) (23.7 vs. 1.5%), fetal distress (36.8 vs. 3.1%), and neonatal intensive care unit (NICU) admission (50.0 vs. 3.1%). Newborns being small for gestational age (SGA) prevalence (13.2 vs. 3.1%), stillbirths (5.3 vs. 3.1%), and neonatal deaths (7.9% vs. 1.5%) showed no significant differences. Conclusions: Idiopathic polyhydramnios is associated with increased risks of preterm delivery, Cesarean section (CS) delivery, neonatal distress, and maternal hemorrhage, highlighting the need for vigilant prenatal care and availability of neonatal intensive care.

Psychological distress and pregnancy outcomes in early-stage gestational hypertension: a case-control study from China

2025-06-20

Xilian Li , Rongmin Wang , Xianfeng Xia +3 more | PeerJ

This study aimed to elucidate the pathophysiological role of psychological distress in early-stage gestational hypertension (GH) through comprehensive assessment of its regulatory effects on disease progression and association with adverse … This study aimed to elucidate the pathophysiological role of psychological distress in early-stage gestational hypertension (GH) through comprehensive assessment of its regulatory effects on disease progression and association with adverse pregnancy outcomes, thereby providing evidence-based support for early screening and intervention strategies. We conducted a prospective case-control study involving 446 patients with early-stage GH (diagnostic criteria: new-onset hypertension after 20 weeks of gestation, blood pressure ≥140/90 mmHg without proteinuria) and 200 normotensive pregnant women as controls. Psychological distress was assessed using the Self-Rated Anxiety Scale (SAS). A multidimensional statistical approach, including univariate analysis and multivariate logistic regression, was employed to systematically explore the risk factors that influence psychological distress. Pregnancy and perinatal outcomes were compared using Chi-square tests and t-tests. The study revealed a markedly elevated prevalence of psychological distress in the early-stage GH group (20.9%) compared to controls (7.0%, P < 0.05). Multivariate analysis identified educational level (OR = 2.298, 95% CI [1.289-4.097]), history of adverse pregnancy (OR = 2.604, 95% CI [1.342-5.050]), and GH itself (OR = 1.859, 95% CI [1.213-2.850]) as independent risk factors for psychological distress. Follow-up data demonstrated that patients with psychological distress exhibited significantly higher rates of progression to preeclampsia (24.7% vs. 12.7%, P < 0.05), along with increased incidence of adverse pregnancy outcomes, including premature rupture of membranes, postpartum hemorrhage, neonatal infection, macrosomia, and low birth weight. This study provides a systematic characterization of psychological distress patterns in early stage GH patients and their potential impact on disease progression. Findings highlight the critical importance of integrating routine psychological screening and early intervention strategies into prenatal care for patients with GH to optimize maternal and neonatal outcomes.

A Changepoint Detection-Based General Methodology for Robust Signal Processing: An Application to Understand Preeclampsia’s Mechanisms

2025-06-19

Patricio Cumsille , Felipe Troncoso , Hermes Sandoval +2 more | Bioengineering

Motivated by illuminating the underlying mechanisms of preeclampsia, we develop a changepoint detection-based general and versatile methodology that can be applied to any experimental model, effectively addressing the challenges of … Motivated by illuminating the underlying mechanisms of preeclampsia, we develop a changepoint detection-based general and versatile methodology that can be applied to any experimental model, effectively addressing the challenges of high uncertainty produced by experimental interventions, intrinsic high variability, and rapidly and abruptly varying time dynamics in perfusion signals. This methodology provides a systematic and reliable approach for robust perfusion signal analysis. The main innovation of our methodology is a highly efficient automatic data processing system consisting of modular programming components. These components include a signal processing tool for optimal segmentation of perfusion signals by isolating their "genuine" vascular response to experimental interventions, and a novel and suitable normalization to evaluate this response concerning an experimental reference state, typically basal or pre-intervention. In this way, we can identify anomalies in an experimental group compared to a control group by disaggregating noise during the transitions just after experimental interventions. We have successfully applied our general methodology to perfusion signals measured from a preeclampsia-like syndrome model developed by our research group. Our findings revealed impaired brain perfusion in offspring from preeclampsia, particularly dysfunctional brain perfusion signals with inadequate perfusion signal vasoreactivity to thermal physical stimuli. This general methodology represents a significant step towards a systematic, accurate, and reliable approach to robust perfusion signals analysis across various experimental settings with diverse intervention protocols.

Routine mid-gestational prediction of later preeclampsia

2025-06-19

Britt Kempener , Emma B. N. J. Janssen , Jonas Ellerbrock +7 more | Best Practice & Research Clinical Obstetrics & Gynaecology

Preeclampsia is thought to be superimposed upon cardiovascular and cardiometabolic risk factors, predominantly consistent with the metabolic syndrome. In this study, we developed and internally validated a prediction model for … Preeclampsia is thought to be superimposed upon cardiovascular and cardiometabolic risk factors, predominantly consistent with the metabolic syndrome. In this study, we developed and internally validated a prediction model for the development of later preeclampsia in pregnant women at routine second-trimester oral glucose tolerance testing. Data were collected during a prospective clinical cohort study, including pregnant women undergoing routine gestational diabetes mellitus (GDM) screening. Routine clinical data during the GDM screening (e.g., oral glucose tolerance test) were considered as potential predictors. Univariable and multivariable logistic regression with Backward Wald elimination were performed to develop the prediction model. Internal validation was performed using bootstrapping. Predictive performance of the final model was evaluated in terms of discrimination and calibration, both before and after adjusting for overfitting. Of 3227 pregnant women undergoing GDM screening, 137 (4.2 %) subsequently developed preeclampsia. The final prediction model included obstetric history of preeclampsia (yes/no), history of large for gestational age (yes/no), current antihypertensive drug use (yes/no), diastolic blood pressure (mmHg), fasting serum creatinine (μmol/l), fasting serum triglycerides (mmol/l), and urinary protein-creatinine ratio (g/mol creatinine). The area under the receiver operating characteristic curve of the model was 0.79 before and after internal validation, with good model calibration. Upon external validation and impact analysis, the proposed second-trimester preeclampsia prediction model enables accurate estimation of individuals risk on predominantly later third trimester development of preeclampsia. The model could facilitate timely, tailored monitoring and early intervention among pregnant women at risk to improve pregnancy outcomes.

Association between blood essential metal elements in early pregnancy and gestational diabetes mellitus

2025-06-19

Guozhen Chen , Li Wu , Cunwei Ji +2 more | Frontiers in Nutrition

Objectives The purpose was to assess the levels of iron (Fe), magnesium (Mg), copper (Cu), calcium (Ca), zinc (Zn) in the blood of pregnant women during early pregnancy, and to … Objectives The purpose was to assess the levels of iron (Fe), magnesium (Mg), copper (Cu), calcium (Ca), zinc (Zn) in the blood of pregnant women during early pregnancy, and to evaluate their potential association with gestational diabetes mellitus (GDM). Methods We enrolled 9,112 pregnant women who underwent testing for essential metal elements at Guangdong Women and Children Hospital during the first trimester in 2015–2022. The basic information of pregnant women and peripheral blood samples were collected, and five essential metal elements in whole blood were detected by atomic absorption spectrometry. The relationship between these essential metal elements and GDM was analyzed using the generalized linear regression model (GLM), weighted quantile sum regression (WQS), quantile g-computation regression (QGC), and Bayesian kernel machine regression (BKMR). Results Analysis of the correlation between essential metal elements and GDM revealed significant associations. Compared with the first quantile concentration level, the fourth quantile level of Fe ( OR = 1.347, 95% CI : 1.158 ~ 1.568), Zn ( OR = 1.379, 95% CI : 1.185 ~ 1.606) and Mg ( OR = 1.192, 95% CI : 1.022 ~ 1.392) exhibited significant associations with GDM. Restricted cubic spline (RCS) analysis showed a positive linear relationship between Fe, Zn, and Mg and GDM risk ( P overall &lt; 0.05 and P non-linear &gt; 0.05). WQS analysis showed that the WQS index had a significant positive correlation with GDM ( OR = 1.129, 95% CI : 1.023 ~ 1.247), with Fe (0.446) having greater weight. QGC analysis revealed a positive correlation between the combined action of five essential metal elements and GDM risk ( OR = 1.161, 95% CI : 1.075 ~ 1.248), with Zn (0.454) and Fe (0.417) showing greater influence. In BKMR analysis, the combined effect of all essential metal elements on GDM showed an overall upward trend, with Fe (PIP = 0.772) having the most significant influence. No interaction between essential metal elements and GDM was found in this study. Conclusion Higher levels of Fe, Zn and Mg were positively correlated with GDM risk. The combined action of five essential metal elements was positively correlated with GDM, with Fe identified as playing the most significant role.

2D Shear Wave Elastography: An Evolving Technique for Comparison of Placental Elasticity in Normal and Preeclamptic Pregnancy

2025-06-19

Ritika Sihmar , Shahina Bano , Renuka Malik | Indian journal of radiology and imaging - new series/Indian journal of radiology and imaging/Indian Journal of Radiology & Imaging

Abstract This article evaluates differences in placental elasticity between normal and preeclamptic pregnancies using shear wave elastography and assesses the potential of the placental elasticity values in predicting preeclampsia. The … Abstract This article evaluates differences in placental elasticity between normal and preeclamptic pregnancies using shear wave elastography and assesses the potential of the placental elasticity values in predicting preeclampsia. The study included 60 pregnant women, 30 diagnosed with preeclampsia and 30 with normal pregnancies, in their second and third trimesters. Shear wave elastography was performed to assess placental elasticity. Both mean (average) and maximum elasticity values were recorded and cutoff values were determined using receiver operating characteristic (ROC) curve analysis to evaluate their potential in predicting preeclampsia. Placental elasticity values were significantly higher in preeclamptic women (group A) compared with healthy pregnant women (group B). The mean elasticity in group A was 15.74 ± 3.51 kPa, with a maximum elasticity of 27.4 ± 4.66 kPa; whereas in group B, the corresponding values were 4.42 ± 1.93 and 7.13 ± 3.05 kPa, respectively (p < 0.0001). In preeclampsia cases, the shear wave modulus was higher in the central region of the placenta than at the edges. ROC curve analysis evaluated a mean elasticity cutoff value of 8.1 kPa, with a sensitivity of 100%, specificity of 96.67%, positive predictive value of 96.8%, negative predictive value of 100%, and a diagnostic accuracy of 98.33%. The study revealed significant differences in placental elasticity between preeclamptic and healthy pregnancies, highlighting the potential of shear wave elastography as a valuable tool for early prediction of preeclampsia. Early prediction using this method could significantly reduce maternal and perinatal mortality and morbidity, especially in developing countries, by identifying cases before the onset of clinical symptoms.

Antenatal identification of early- and late-onset fetal growth restriction and the possible impact of the introduction of cerebroplacental ratio: Effect on perinatal and childhood outcome

2025-06-18

Emma Hertting , Lotta Herling , Pelle G. Lindqvist +1 more | PLoS ONE

Objective To investigate the effect of antenatal identification of small for gestational age (SGA) fetuses on perinatal and childhood outcomes, separately analyzing early- and late-onset fetal growth restriction (FGR). Materials … Objective To investigate the effect of antenatal identification of small for gestational age (SGA) fetuses on perinatal and childhood outcomes, separately analyzing early- and late-onset fetal growth restriction (FGR). Materials and methods A register-based cohort study of all newborns born SGA, delivered in Stockholm in 2014 and 2017, n = 5499. Ultrasound reports of fetuses born SGA were reviewed and fetuses identified as SGA with ultrasound before birth were further defined as early- or late-onset FGR according to established criteria. Data from the medical chart for maternity and delivery was linked to nationwide Swedish registers. Adverse outcomes for antenatally non-identified SGA/FGR newborns and fetuses identified as early- or late-onset FGR were compared using logistic regression models. A composite outcome, severe adverse outcome, was constructed and defined as at least one of the following: stillbirth, severe newborn distress, severe neonatal outcome, severe childhood outcome. Individual components of the composite outcome were analyzed as secondary outcomes. Results Identified early-onset FGR fetuses had an increased risk for severe adverse outcome, compared to non-identified SGA/FGR (aOR 1.81, 95% CI 1.25–2.61), in contrast to late-onset FGR fetuses (aOR 1.14, 95% CI 0.78–1.67). Identified early-onset FGR had a decreased risk of stillbirth (aOR 0.47, 95% CI 0.23–0.96), an increased risk of severe newborn distress (aOR 2.80, 95% CI 1.79–4.39) and severe childhood outcome (aOR 3.00, 95% CI 1.51–5.94), compared to non-identified SGA/FGR. Identified late-onset FGR was only associated with an increased risk of severe childhood outcome (aOR 1.91, 95% CI 1.04–3.52). Conclusion Identified early-onset FGR fetuses benefited from identification with a decreased risk of stillbirth at the price of an increased risk for severe newborn and childhood outcomes. For late-onset FGR the advantages were undetectable; identification was associated with an increased risk for severe childhood outcome, while the negative association with stillbirth did not reach significance.

Corrigendum to “Identification of divergent placental profiles in clinically distinct pregnancy complications revealed by the transcriptome” [Placenta 154 (2024): 184–192 / PMID: 39042974]

2025-06-18

Camille Couture , Maxime Caron , Pascal St-Onge +4 more | Placenta

Role of vitamin D in the pathogenesis of early-onset preeclampsia: a narrative review

2025-06-18

Shu Zheng , Shuai Dong , Huimin Shen +2 more | Frontiers in Nutrition

Early-onset Preeclampsia (EOPE) is a severe pregnancy complication that poses significant risks to both maternal and fetal health, often leading to fetal growth restriction and maternal morbidity. Despite extensive research, … Early-onset Preeclampsia (EOPE) is a severe pregnancy complication that poses significant risks to both maternal and fetal health, often leading to fetal growth restriction and maternal morbidity. Despite extensive research, the etiology of EOPE remains unclear, though emerging evidence suggests that vitamin D (VD) may play an important role in placental development and function. Recent studies associate VD deficiency with adverse pregnancy outcomes, including EOPE, through mechanisms such as impaired trophoblast invasion and immune dysregulation at the maternal-fetal interface. This review aimed to synthesize current literature on the role of VD in the pathogenesis of EOPE. We reviewed in vitro , in vivo , and clinical studies to evaluate the impact of VD on immune modulation, angiogenesis, oxidative stress, and trophoblast migration and invasion in the placenta. This comprehensive review aims to provide insights into how VD deficiency exacerbates placental dysfunction, contributing to the development of EOPE. These insights support the rationale for VD supplementation as a potential preventive strategy and highlight the need for further clinical investigation.

PiggyBac Transposase Mediated Inducible Trophoblast-specific Knockdown of Mtor Decreases Placental Nutrient Transport and Fetal Growth

2025-06-18

Fredrick J. Rosario , Johann Urschitz , Haide Razavy +3 more | Clinical Science

Abnormal fetal growth is associated with perinatal complications and adult disease. The placental mechanistic target of rapamycin (mTOR) signaling activity is positively correlated to placental nutrient transport and fetal growth. … Abnormal fetal growth is associated with perinatal complications and adult disease. The placental mechanistic target of rapamycin (mTOR) signaling activity is positively correlated to placental nutrient transport and fetal growth. However, if this association represents a mechanistic link, it remains unknown. We hypothesized that trophoblast-specific Mtor knockdown in late pregnant mice decreases trophoblast nutrient transport and inhibits fetal growth. PiggyBac Transposase-Enhanced Pronuclear Injection was performed to generate transgenic mice containing a trophoblast-specific Cyp19I.1 promoter-driven, doxycycline-inducible luciferase reporter transgene with a Mtor shRNAmir sequence in its 3’ untranslated region (UTR). We induced Mtor knockdown by administration of doxycycline starting at E14.5. Dams were euthanized at E 17.5, and trophoblast-specific gene targeting was confirmed. Placental mTOR protein expression was reduced in these animals, which was associated with a marked inhibition of mTORC1 and mTORC2 signaling activity. Moreover, we observed a decreased expression of System A amino acid transporter isoform SNAT2 and the System L amino acid transporter isoform LAT1 in isolated trophoblast plasma membranes and lower fetal, placental weight and fetal: placental weight ratio. We also silence the MTOR in cultured primary human trophoblast cells, which inhibited the mTORC1 and C2 signaling, System A and System L amino acid transport activity, and markedly decreased the trafficking of LAT1 and SNAT2 to the plasma membrane. Inhibition of trophoblast mTOR signaling in late pregnancy is mechanistically linked to decreased placental nutrient transport and reduced fetal growth. Modulating trophoblast mTOR signaling may represent a novel intervention in pregnancies with abnormal fetal growth.

The Amsterdam Criteria and beyond: development of a Standardized Structured Reporting (SSR) tool for diagnosis of placental pathology

2025-06-18

Ekaterina Bazyleva , Lotte E. van der Meeren , Mirthe H. Schoots +5 more | Virchows Archiv

Abstract The lack of standardized reporting in placental pathology limits research scalability and clinical application despite consensus-based criteria like the Amsterdam Criteria. This study presents the development and implementation of … Abstract The lack of standardized reporting in placental pathology limits research scalability and clinical application despite consensus-based criteria like the Amsterdam Criteria. This study presents the development and implementation of a comprehensive Standardized Structured Reporting (SSR) tool for placental pathology. Utilizing the LogicNets© platform, the tool incorporates the Amsterdam Criteria, Freedman placental phenotype classification system, and consensus recommendations on placental examination. Development involved collaboration with placental pathology experts, literature review, and iterative feedback from pathologists to address reporting inconsistencies and ensure practicality. The SSR tool integrates evidence-based standards for examining and phenotyping the placenta, including structured gross and microscopic analyses. It introduces control mechanisms for severity grading and phenotype assignment, enabling precise assessment of placental lesions, even in multiple births. Organized into sections—Demographics, Macroscopy, Microscopy, and Group and Phenotype—it efficiently records and analyzes data. Additional functionalities include automated calculations of gross placental features, built-in controls, and versatile documentation of microscopic observations. The tool is designed for seamless integration into clinical workflows. Implementing the SSR tool could enhance placental pathology reporting quality, completeness, and consistency, facilitating large-scale analyses. Discrete data capture enables robust research, potentially improving the clinical utility and understanding of placenta-mediated diseases. However, further validation is required before widespread adoption. Embracing SSR could standardize placental examination, improve clinical interpretation, and advance research in placental pathology for enhanced utility in both research and clinical care.

Placental Syncytium‐on‐Chip (PSoC)–Comparison of Forskolin or Mechanical Induced‐Syncytialization

2025-06-18

Ludivine Delon , Mathias Busek , Pedro Duarte Menezes +7 more | Advanced Healthcare Materials

Abstract The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts … Abstract The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts and differentiated syncytiotrophoblats, whose maturation and function are influenced by wall shear stress (WSS) from the maternal blood circulation. Most in vitro placenta models rely on cyclic adenosine monophosphate inducer forskolin (FSK) to establish a placental syncytium. Here a trophoblastic BeWo cell line is used to systematically compare the effect of FSK treatment in static culture with WSS stimulation in a pumpless, recirculating organ‐on‐chip. It is shown that BeWo cells undergo a similar differentiation under WSS exposure to FSK treatment. A WSS of 0.1 dyn cm −2 leads to cell fusion, polarization, barrier functions, human chorionic gonadotropin (β‐hCG) secretion, and increased expression of key transporters. Moreover, WSS induces favorable changes in the levels of FMS‐like tyrosine kinase‐1 (FLT‐1) and Placental Growth Factor (PlGF) suggesting the development of a physiologically relevant placental syncytium‐on‐chip (PSoC) without the need for FSK. The platform is further expanded to a syncytiotrophoblast/endothelial co‐culture showing physiological vascular functions under WSS. The forskolin‐free PSoC presented here represents the first pumpless recirculating and scalable platform for physiological placental studies and drug testing.

Physical activity pattern and Pre-eclampsia risk biomarkers: an observational study

2025-06-18

Ana Martinez Cagiao , Pablo Aleixandre Diaz Brage , Manuel-Avelino Giráldez +3 more | Reproductive Biology

Decoding placental dysfunction with a new angiogenic classification of PlGF and sFlt-1

2025-06-18

Valentina Giardini , Alice Santagati , Elisabetta Marelli +4 more | European Journal of Obstetrics & Gynecology and Reproductive Biology

The ratio between sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (Placental Growth Factor) was recently introduced to aid in the management of hypertensive disorders of pregnancy and fetal growth restriction, … The ratio between sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (Placental Growth Factor) was recently introduced to aid in the management of hypertensive disorders of pregnancy and fetal growth restriction, but it has limitations. This study proposes a new angiogenic classification of PlGF and sFlt-1 to enhance maternal and fetal risk assessment in pregnancies with suspected placental dysfunction. A retrospective analysis was conducted on hospitalized singleton pregnancies beyond the 20th week complicated by hypertensive disorders of pregnancy and/or fetal growth restriction. Patients were classified based on sFlt-1/PlGF (low, medium, high, very high) and into the nine possible combinations using PlGF and sFlt-1 gestational age-specific levels: (1) PlGF and sFlt-1 within range; (2) PlGF in range, sFlt-1 < range; (3) PlGF in range, sFlt-1 > range; (4) PlGF < range, sFlt-1 in range; (5) PlGF and sFlt-1 < range; (6) PlGF < range, sFlt-1 > range; (7) PlGF > range, sFlt-1 in range; (8) PlGF > range, sFlt-1 < range; (9) PlGF and sFlt-1 > range. The cohort included 227 patients. The most common categories were 1, 3, 4, and 6. Categories 4 and 6 had a higher proportion of fetal growth restriction, whereas categories 3 and 6, presented a greater risk of severe maternal complications. Category 6 exhibited the highest risk of adverse maternal-fetal outcomes; conversely, category 1 was the category at the lowest risk for complications. Notably, 40 % of patients classified as low or medium risk by the sFlt-1/PlGF were high-risk by our classification. Evaluation of actual PlGF and sFlt-1 levels rather than set cut-off ratios can improve the risk stratification of clinical manifestations of placental pathology.

Genetic expression of NKX2-5 gene among first trimester pregnancy loss

2025-06-18

M. S. Dhanya , S Karthick , Reba Babu Alex +5 more | Human Gene