Fetal growth restriction as the initial finding of preeclampsia is a clinical predictor of maternal and neonatal prognoses: a single-center retrospective study.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder specific to pregnancy that can cause severe maternal-neonatal complications. The International Society for the Study of Hypertension in Pregnancy revised the PE criteria in 2018; a PE diagnosis can be established in the absence of proteinuria when organ or uteroplacental dysfunction occurs. The initial findings of PE (IFsPE) at the first diagnosis can vary considerably across patients. However, the impacts of different IFsPE on patient prognoses have not been reported. Thus, we investigate the predictors of pregnancy complications and adverse pregnancy outcomes based on IFsPE according to the new criteria. METHODS: This retrospective study included 3729 women who delivered at our hospital between 2015 and 2019. All women were reclassified based on the new PE criteria and divided into three groups based on the IFsPE: Classification 1 (C-1), proteinuria (classical criteria); Classification 2 (C-2), damage to other maternal organs; and Classification 3 (C-3), uteroplacental dysfunction. Pregnancy complications and adverse pregnancy outcomes were assessed and compared among the three groups. RESULTS: In total, 104 women with PE were included. Of those, 42 (40.4%), 28 (26.9%), and 34 (32.7%) were assigned to C-1, C-2, and C-3 groups, respectively. No significant differences in maternal characteristics were detected among the three groups, except for gestational age at PE diagnosis (C-1, 35.5 ± 3.0 weeks; C-2, 35.2 ± 3.6 weeks; C-3, 31.6 ± 4.6 weeks, p <  0.01). The rates of premature birth at < 37 weeks of gestation, fetal growth restriction (FGR), and neonatal acidosis were significantly higher in the C-3 group compared to the C-1 and C-2 groups. Additionally, the composite adverse pregnancy outcomes of the C-3 group compared with C-1 and C-2 represented a significantly higher number of patients. CONCLUSIONS: PE patients with uteroplacental dysfunction as IFsPE had the most unfavorable prognoses for premature birth, FGR, acidosis, and composite adverse pregnancy outcomes.

Subtypes of Preeclampsia: Recognition and Determining Clinical Usefulness.

The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of inflammation, oxidative and endoplasm reticulum stress, and angiogenic dysfunction. Yet, we have not progressed greatly toward clinically useful prediction nor had substantial success in prevention or treatment. One possibility is that the maternal syndrome may be reached through different pathophysiological pathways, that is, subtypes of preeclampsia, that in their specificity yield more clinical utility. For example, early and late onset preeclampsia are increasingly acknowledged as different pathophysiological processes leading to a common presentation. Other subtypes of preeclampsia are supported by disparate clinical outcomes, long-range prognosis, organ systems involved, and risk factors. These insights have been supplemented by discovery-driven methods, which cluster preeclampsia cases into groups indicating different pathophysiologies. In this presentation, we review likely subtypes based on current knowledge and suggest others. We present a consideration of the requirements for a clinically meaningful preeclampsia subtype. A useful subtype should (1) identify a specific pathophysiological pathway or (2) specifically indicate maternal or fetal outcome, (3) be recognizable in a clinically useful time frame, and (4) these results should be reproducible and generalizable (but at varying frequency) including in low resource settings. We recommend that the default consideration be that preeclampsia includes several subtypes rather than trying to force all cases into a single pathophysiological pathway. The recognition of subtypes and deciphering their different pathophysiologies will provide specific targets for prevention, prediction, and treatment directing personalized care.

The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study.

BACKGROUND: The diagnostic criteria for preeclampsia have evolved from the traditional definition of de novo hypertension and proteinuria to a broader definition of hypertension with evidence of end-organ dysfunction. Although this change is endorsed by various societies such as the International Society for the Study of Hypertension in Pregnancy and the American College of Obstetricians and Gynecologists, there remains controversy with regard to the implementation of broader definitions and the most appropriate definition of end-organ dysfunction. OBJECTIVE: This study aimed to assess the impact of different diagnostic criteria for preeclampsia on rates of disease diagnosis, disease severity, and adverse outcomes and to identify associations between each component of the different diagnostic criteria and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies at Monash Health between January 1, 2016 and July 31, 2018. Within this population, all cases of gestational hypertension and preeclampsia were reclassified according to the International Society for the Study of Hypertension in Pregnancy 2001, American College of Obstetricians and Gynecologists 2018, and International Society for the Study of Hypertension in Pregnancy 2018 criteria. Differences in incidence of preeclampsia and maternal and perinatal outcomes were compared between the International Society for the Study of Hypertension in Pregnancy 2001 group and the extra cases identified by American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018. Outcomes assessed included biochemical markers of preeclampsia, a composite of adverse maternal outcomes, and a composite of adverse perinatal outcomes. Multiple logistic regression analysis was also performed to assess each component of the American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018 criteria and their associations with adverse maternal and perinatal outcomes. RESULTS: Of 22,094 pregnancies, 751 (3.4%) women had preeclampsia as defined by any of the 3 criteria. Compared with International Society for the Study of Hypertension in Pregnancy 2001, the American College of Obstetricians and Gynecologists 2018 criteria identified an extra 42 women (n=654 vs n=696, 6.4% relative increase) with preeclampsia, and International Society for the Study of Hypertension in Pregnancy 2018 identified an extra 97 women (n=654 vs n=751, 14.8% relative increase). The additional women identified by International Society for the Study of Hypertension in Pregnancy 2018 exhibited a milder form of disease with lower rates of severe hypertension (62.4% vs 44.3%; P<.01) and magnesium sulfate use (11.9% vs 4.1%; P<.05) and a trend toward lower rates of adverse maternal outcomes (9.8% vs 4.1%). These women also delivered at a later gestation, and their babies had a lower number of neonatal intensive care unit admissions and adverse perinatal outcomes. Objective features such as fetal growth restriction, thrombocytopenia, renal and liver impairment, and proteinuria were associated with an increased risk of adverse maternal and perinatal outcomes, whereas subjective neurologic features demonstrated poorer associations. CONCLUSION: Implementation of broader definitions of preeclampsia will result in an increased incidence of disease diagnosis. However, because women who exclusively fulfill the new criteria have a milder phenotype of the disease, it remains uncertain whether this will translate to improved outcomes.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Maternal preeclampsia and long-term infectious morbidity in the offspring - A population based cohort analysis.

OBJECTIVE: We evaluated the association between maternal preeclampsia and long-term infectious morbidity of the offspring. STUDY DESIGN: A retrospective cohort analysis was performed, evaluating risk of long-term infectious morbidity in children born to women with and without preeclampsia between the years 1991-2014. Infectious morbidity included hospitalizations of offspring during childhood. Infants were followed until age 18 years or until hospitalization. Multiple gestations, newborns with congenital malformations and perinatal deaths were excluded. Cumulative incidence rates of infectious morbidity were compared. A Cox proportional hazards model was employed to control for various confounders including gestational age and cesarean delivery (CD). RESULTS: During the study period 239,725 newborns were included: 96% (n = 230,217) without preeclampsia, 3% (n = 7280) with mild preeclampsia and 0.9% (n = 2228) with severe preeclampsia, defined mostly by evidence of maternal organ dysfunction. Hospitalization rate due to infectious morbidity was significantly higher for offspring to mothers with severe preeclampsia in comparison to those with no preeclampsia (13.1% vs 11%, P = 0.008), specifically respiratory and bacterial infections. The Kaplan-Meier survival curve demonstrated that offspring born to mothers with severe preeclampsia had a significantly higher cumulative incidence of hospitalization (Log-rank test P value = 0.026). However, while controlling for confounders in the Cox regression model, severe preeclampsia was not found as an independent risk factor (adjusted hazard ratio 0.95, 95% confidence interval 0.8-1.1, P = 0.36). CONCLUSION: While severe preeclampsia is associated with higher risk for long-term infectious morbidity of the offspring, it seems that the association is due to prematurity and CD, but not the preeclampsia per-se.

Multiplex Analysis of Circulating Maternal Cardiovascular Biomarkers Comparing Preeclampsia Subtypes.

Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery

Analyzing Preeclampsia as the Tip of the Iceberg Represented by Women with Long-Term Cardiovascular Disease, Atherosclerosis, and Inflammation.

PURPOSE OF REVIEW: Cardiovascular and endothelial dysfunction is recognized nowadays as an important etiological factor contributing to the development of hypertensive disorders of pregnancy. RECENT FINDINGS: Preeclampsia is considered a specific disease of pregnancy, but recent theories suggest that women suffering from the condition have greater propensity to develop atherosclerosis, heart disease, and stroke over the years. It is possible that transient but severe endothelial dysfunction observed in preeclampsia potentiates a cascade of events that progresses to atherosclerosis. Preeclampsia offers a unique window of opportunity to identify maternal endothelial dysfunction and pre-existing cardiovascular disease. The placenta is closely involved in the onset of preeclampsia, but endothelial and cardiac vascular factors also play important causal roles in the development of hypertension during pregnancy. According to the data presented, it is clear that preeclampsia selects a group at high risk of development of atherosclerosis and at increased cardiovascular risk, as well as of stroke, in the decades following childbirth.

Desenlaces materno-fetales de los embarazos con trastornos hipertensivos: un estudio transversal / Maternal and fetal outcomes of pregnancies with hypertensive disorders: a cross-sectional study

INTRODUCCIÓN Y OBJETIVO: Los trastornos hipertensivos asociados al embarazo son considerados un problema de salud pública. Se busca describir las características clínicas y desenlaces materno-fetales de las pacientes con esta patología, atendidas en el Hospital Universitario de Santander (HUS) durante el primer semestre de 2017. MÉTODOS: Estudio observacional retrospectivo de corte transversal. Se incluyeron las pacientes en estado de embarazo o puerperio con diagnóstico o sospecha de trastorno hipertensivo; se excluyeron aquellas que no pudieron ser clasificadas o no correspondían a éstos. RESULTADOS: Se analizaron 181 historias clínicas; la edad de las pacientes osciló entre 14 y 44 años; el 43,7% eran primigestantes; el 40,3% tuvo un control prenatal inadecuado y el 27,5% tenía antecedente de trastorno hipertensivo en gestaciones previas. El 75,1% de las pacientes fueron clasificadas como preeclampsia, 18,2% con hipertensión gestacional, 4,4% con hipertensión más preeclampsia sobreagregada y 2,2% con hipertensión crónica. El 16,9% de las pacientes con preeclampsia debutaron antes de la semana 34, de las cuales el 91,3% tenían criterios de severidad; mientras que entre las demás, el 84% presentaron criterios de severidad. CONCLUSIONES: La preeclampsia fue el trastorno hipertensivo más frecuente, predominó la presentación tardía y severa con importantes tasas de complicación maternas y fetales. Mediante la implementación de estrategias de detección temprana y adecuada atención de los trastornos hipertensivos asociados al embarazo podrían mejorarse los desenlaces materno-fetales.

BACKGROUND AND OBJECTIVE: Hypertensive disorders of pregnancy are considered a public health issue. The aim is to describe the clinical features, maternal - fetal outcomes of patients with this disease, who were admitted at the University Hospital of Santander (Bucaramanga, Colombia) during the first half of 2017. METHOD: Cross-sectional retrospective observational study. Patients in pregnancy or puerperium with diagnosis of hypertensive disorder were included; those who could not be classified or did not correspond were excluded. RESULTS: 181 clinical charts were analyzed, the age of the patients ranged between 14 and 44 years, 43.7% were nulliparous, 40.3% had an inadequate prenatal control and 27.5% had history of hypertensive disorder in previous pregnancies. 75.1% were classified as preeclampsia, 18.2% as gestational hypertension, 4.4% as hypertension and superimposed preeclampsia and 2.2% with chronic hypertension; 16.9% of the patients were of an early-onset preeclampsia before week 34, of which 91.3% had criteria of severity; among the others, 84% presented criteria of severity. CONCLUSION: Preeclampsia was the most frequent hypertensive disorder, late and severe presentation prevailed with important maternal and fetal complication rates. Through the implementation of early detection strategies and adequate care of hypertensive disorders associated with pregnancy maternal and fetal outcomes could be improved.

Evaluation of maternal renal cortical elasticity in pregnancies with early- and late-onset preeclampsia.

Objective: The current study aimed to investigate renal cortical elasticity (RCE) in early- and late-onset preeclampsia patients and compare the results with healthy controls.Materials and methods: The study consisted of 136 pregnant women. Three groups were identified as; the late-onset preeclampsia (LOP) group (n = 40), the early-onset preeclampsia (EOP) group (n = 32) and the control group (n = 64). RCE values were measured by point shear wave elastography (pSWE). Nine measurements were taken for each kidney and the mean of nine measurements was accepted as the mean RCE value for each kidney. The arithmetic mean of left and right RCE values was accepted as the overall RCE value of a subject. Groups were compared in terms of clinical and biochemical parameters, ultrasonography findings and pSWE values.Results: There was a statistically significant difference between groups in terms of overall RCE values (F[2,133] = 17.96, p < .001). Post hoc comparisons indicated that both preeclampsia groups exhibited significantly higher RCE values than the control group. However, overall RCE values were not significantly different between the EOP and LOP groups. Overall RCE values were significantly and positively correlated with systolic blood pressure (r = 0.363, p < .001), diastolic blood pressure (r = 0.347, p < .001), proteinuria (r = 0.343, p < .001), serum creatinine level (r = 0.181, p = .035), serum uric acid level (r = 0.243, p = .004) and blood urea nitrogen (r = 0.27, p = .001).Conclusion: Our study demonstrated that maternal renal cortical stiffness increased in women with preeclampsia. The increased RCE values may be indicative for the severity of preeclampsia due to positive correlations between renal cortical stiffness and systolic - diastolic blood pressure and serum creatinine level.

Omega-3 fatty acids differentially influences embryotoxicity in subtypes of preeclampsia.

Background: Early (EOP) and late onset (LOP) preeclampsia are two subtypes of preeclampsia. This study examines the effect of maternal omega-3 fatty acids and vitamin E supplementation in a rat model of preeclampsia.Method: Pregnant Wistar rats were assigned to control; EOP; LOP; EOP+omega-3 fatty acid supplementation+vitamin E and LOP+omega-3 fatty acid supplementation+vitamin E. L-Nitroarginine methylester was used to induce preeclampsia. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d14 and d20 of gestation.Results: Animals from EOP and LOP groups demonstrated higher systolic and diastolic BP, lower weight gain, lower conceptuses size, lower conceptuses weight and fetal weight as compared to control. EOP and LOP groups showed higher percentage of fetal resorptions and embryotoxicity (deformities and hematomas).Conclusion: Supplementation reduced the diastolic BP, percentage of resorptions and embryotoxicity only in the LOP group, suggesting a need for differential supplementation regime for the two subtypes of preeclampsia.

Body of Evidence in Favor of Adopting 130/80 mm Hg as New Blood Pressure Cut-Off for All the Hypertensive Disorders of Pregnancy.

The American College of Cardiology/American Heart Association (ACC/AHA) updated its guideline redefining the classification of hypertension and the blood pressure cut-off in 2017. The current cut-offs for stage 1 hypertension of 130 mm Hg systolic blood pressure or 80 mm Hg diastolic blood pressure replace the previous cut-offs of 140 mm Hg systolic blood pressure or 90 mm Hg diastolic blood pressure which were based on the ACC/AHA guidelines from 1988. However, the blood pressure cut-off for the obstetric population still remains as 140/90 mm Hg despite the scarcity of evidence for it. Recent American College of Obstetricians and Gynecologists (ACOG) bulletins for pregnant women have not reflected the new ACC/AHA change of guideline. We reviewed a mounting body of evidence prompting the implementation of the new ACC/AHA guidelines for the obstetric population. These studies examined maternal and fetal outcomes applying the new ACC/AHA guidelines during antepartum or postpartum care.

Both "canonical" and "immunological" preeclampsia subtypes demonstrate changes in placental immune cell composition.

Our prior work investigating the heterogeneity of preeclampsia identified multiple placental subtypes of this disorder, including a "canonical" group with maternal vascular malperfusion and an "immunological" group with signs of allograft rejection. Here, we perform a pilot immunohistochemistry study to investigate if an increase in infiltrating maternal immune cells is contributing to the "immunological" pathology subtype. This revealed an enrichment of monocytes and/or neutrophils (CD68 + and MPO+ cells) in the intervillous space of these placentas. Surprisingly, "canonical" samples also demonstrated a significant result, with decreased CD68 staining. As such, further immunohistochemistry to assess immune contributions in preeclampsia subtypes is warranted.

Maternal Serum Angiogenic Factor sFlt-1 to PlGF Ratio in Preeclampsia: A Useful Marker for Differential Diagnosis and Prognosis Evaluation in Chinese Women.

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

Pre­eclampsia (PE) is a multisystem disorder that typically affects 2%­5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Globally, 76 000 women and 500 000 babies die each year from this disorder. Furthermore, women in low­resource countries are at a higher risk of developing PE compared with those in high­resource countries. Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two­stage process. The first stage is caused by shallow invasion of the trophoblast, resulting in inadequate remodeling of the spiral arteries. This is presumed to lead to the second stage, which involves the maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in the clinical features of the disorder. Accurate prediction and uniform prevention continue to elude us. The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an "at risk" group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly. PE has been previously defined as the onset of hypertension accompanied by significant proteinuria after 20 weeks of gestation. Recently, the definition of PE has been broadened. Now the internationally agreed definition of PE is the one proposed by the International Society for the Study of Hypertension in Pregnancy (ISSHP). According to the ISSHP, PE is defined as systolic blood pressure at ≥140 mm Hg and/or diastolic blood pressure at ≥90 mm Hg on at least two occasions measured 4 hours apart in previously normotensive women and is accompanied by one or more of the following new­onset conditions at or after 20 weeks of gestation: 1.Proteinuria (i.e. ≥30 mg/mol protein:creatinine ratio; ≥300 mg/24 hour; or ≥2 + dipstick); 2.Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine ≥90 µmol/L; 1 mg/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase >40 IU/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or hematological complications (thrombocytopenia­platelet count <150 000/µL, disseminated intravascular coagulation, hemolysis); or 3.Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth). It is well established that a number of maternal risk factors are associated with the development of PE: advanced maternal age; nulliparity; previous history of PE; short and long interpregnancy interval; use of assisted reproductive technologies; family history of PE; obesity; Afro­Caribbean and South Asian racial origin; co­morbid medical conditions including hyperglycemia in pregnancy; pre­existing chronic hypertension; renal disease; and autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome. These risk factors have been described by various professional organizations for the identification of women at risk of PE; however, this approach to screening is inadequate for effective prediction of PE. PE can be subclassified into: 1.Early­onset PE (with delivery at <34+0 weeks of gestation); 2.Preterm PE (with delivery at <37+0 weeks of gestation); 3.Late­onset PE (with delivery at ≥34+0 weeks of gestation); 4.Term PE (with delivery at ≥37+0 weeks of gestation). These subclassifications are not mutually exclusive. Early­onset PE is associated with a much higher risk of short­ and long­term maternal and perinatal morbidity and mortality. Obstetricians managing women with preterm PE are faced with the challenge of balancing the need to achieve fetal maturation in utero with the risks to the mother and fetus of continuing the pregnancy longer. These risks include progression to eclampsia, development of placental abruption and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. On the other hand, preterm delivery is associated with higher infant mortality rates and increased morbidity resulting from small for gestational age (SGA), thrombocytopenia, bronchopulmonary dysplasia, cerebral palsy, and an increased risk of various chronic diseases in adult life, particularly type 2 diabetes, cardiovascular disease, and obesity. Women who have experienced PE may also face additional health problems in later life, as the condition is associated with an increased risk of death from future cardiovascular disease, hypertension, stroke, renal impairment, metabolic syndrome, and diabetes. The life expectancy of women who developed preterm PE is reduced on average by 10 years. There is also significant impact on the infants in the long term, such as increased risks of insulin resistance, diabetes mellitus, coronary artery disease, and hypertension in infants born to pre­eclamptic women. The International Federation of Gynecology and Obstetrics (FIGO) brought together international experts to discuss and evaluate current knowledge on PE and develop a document to frame the issues and suggest key actions to address the health burden posed by PE. FIGO's objectives, as outlined in this document, are: (1) To raise awareness of the links between PE and poor maternal and perinatal outcomes, as well as to the future health risks to mother and offspring, and demand a clearly defined global health agenda to tackle this issue; and (2) To create a consensus document that provides guidance for the first­trimester screening and prevention of preterm PE, and to disseminate and encourage its use. Based on high­quality evidence, the document outlines current global standards for the first­trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of pre­eclampsia in singleton pregnancy.1 It provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings. Suggestions are provided for a variety of different regional and resource settings based on their financial, human, and infrastructure resources, as well as for research priorities to bridge the current knowledge and evidence gap. To deal with the issue of PE, FIGO recommends the following: Public health focus: There should be greater international attention given to PE and to the links between maternal health and noncommunicable diseases (NCDs) on the Sustainable Developmental Goals agenda. Public health measures to increase awareness, access, affordability, and acceptance of preconception counselling, and prenatal and postnatal services for women of reproductive age should be prioritized. Greater efforts are required to raise awareness of the benefits of early prenatal visits targeted at reproductive­aged women, particularly in low­resource countries. Universal screening: All pregnant women should be screened for preterm PE during early pregnancy by the first­trimester combined test with maternal risk factors and biomarkers as a one­step procedure. The risk calculator is available free of charge at https://fetalmedicine.org/research/assess/preeclampsia. FIGO encourages all countries and its member associations to adopt and promote strategies to ensure this. The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI). Where it is not possible to measure PLGF and/or UTPI, the baseline screening test should be a combination of maternal risk factors with MAP, and not maternal risk factors alone. If maternal serum pregnancy­associated plasma protein A (PAPP­A) is measured for routine first­trimester screening for fetal aneuploidies, the result can be included for PE risk assessment. Variations to the full combined test would lead to a reduction in the performance screening. A woman is considered high risk when the risk is 1 in 100 or more based on the first­trimester combined test with maternal risk factors, MAP, PLGF, and UTPI. Contingent screening: Where resources are limited, routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of PLGF and UTPI for a subgroup of the population (selected on the basis of the risk derived from screening by maternal factors and MAP) can be considered. Prophylactic measures: Following first­trimester screening for preterm PE, women identified at high risk should receive aspirin prophylaxis commencing at 11­14+6 weeks of gestation at a dose of ~150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed. Low­dose aspirin should not be prescribed to all pregnant women. In women with low calcium intake (<800 mg/d), either calcium replacement (≤1 g elemental calcium/d) or calcium supplementation (1.5­2 g elemental calcium/d) may reduce the burden of both early­ and late­onset PE.

Increase in the number of patients diagnosed using the new classification of hypertensive disorders of pregnancy in Japan.

AIM: This study aimed to examine how the number of patients diagnosed with pre-eclampsia increased according to the Japanese classification of hypertensive disorders of pregnancy (HDP) that was revised in 2018. The effect of new classification on perinatal outcomes was also analyzed. METHODS: We enrolled 181 women with HDP who delivered at Hokkaido University Hospital between February 2011 and December 2017. All women were reclassified on the basis of the new classification, in which proteinuria was not required to diagnose pre-eclampsia in patients with maternal organ damage. The number and reasons of reclassification and the admission rate to the neonatal intensive care unit (NICU) and gestational age (GA) at the onset of HDP and at delivery were analyzed. RESULTS: In this cohort, 17 (9.4%) of 181 women with HDP were reclassified. Low platelet count (41.2%) and uteroplacental dysfunction (41.2%) were the two main causes for reclassification. GA at the onset of HDP (33.6 [29.9-36.1] weeks vs 37.4 [35.7-38.4] weeks; P < 0.001) and at delivery (35.9 [32.4-37.3] weeks vs 38.1 [37.3-39.6] weeks; P < 0.001) were significantly earlier in women with reclassification than women without reclassification. The NICU admission rate was higher in women with reclassification than women without reclassification (70.6% vs 20.4%; P < 0.001). CONCLUSION: Almost 10% of pregnant women were newly diagnosed with pre-eclampsia as per the new Japanese classification of HDP. Women with reclassification as pre-eclampsia had a greater risk of preterm delivery and NICU admission than those who were not reclassified.

Trends in comorbidity, acuity, and maternal risk associated with preeclampsia across obstetric volume settings.

OBJECTIVE: The objective of this study was to characterize morbidity, acuity, and maternal risks associated with preeclampsia across hospitals with varying obstetric volumes. METHODS: This retrospective cohort analysis used a large administrative data source, the Perspective database, to characterize the risk for preeclampsia from 2006 to 2015. Hospitals were classified as having either low (≤1000), moderate (1001-2000), or high (≥2000) delivery volume. The primary outcomes included preeclampsia, antihypertensive administration, comorbidity, and related severe maternal morbidity. Severe maternal morbidity was estimated using criteria from the Centers for Disease Control and Prevention. Comorbidity was estimated using an obstetric comorbidity index. Univariable comparisons were made with Chi-squared test. Adjusted log linear regression models were fit to assess factors associated with severe morbidity with risk ratios with 95% confidence intervals as the measures of effect. Population weights were applied to create national estimates. RESULTS: Of 36,985,729 deliveries included, 1,414,484 (3.8%) had a diagnosis of preeclampsia. Of these, 779,511 (2.1%) had mild, 171,109 (0.5%) superimposed, and 463,864 (1.3%) severe preeclampsia. The prevalence of mild, superimposed, and severe preeclampsia each increased over the study period with severe and superimposed preeclampsia as opposed to mild preeclampsia increasing the most proportionately (53.2 and 102.5 versus 10.8%, respectively). The use of antihypertensives used to treat severe range hypertension increased with use of intravenous labetalol increasing 31.5%, 43.2%, and 36.1% at low-, medium-, and high-volume hospitals. Comorbid risk also increased across hospital volume settings as did risk for severe maternal morbidity. CONCLUSIONS: Preeclampsia is increasing across obstetric care settings with preeclamptic patients demonstrating increasing comorbid risk, increased risk for severe morbidity, and more frequent need for treatment of acute hypertension.

Characteristics and outcome of severe preeclampsia/eclampsia concurrent with or complicated by acute pancreatitis: a report of five cases and literature review.

OBJECTIVE: The objective of this study is to determine the rate of acute pancreatitis in preeclampsia/eclampsia patients and describe the clinical manifestations, treatment characteristics and outcome of five cases of severe preeclampsia concurrent with or complicated by acute pancreatitis. METHODS: The clinical data of pregnant women with preexisting or gestational hypertension who sought medical care between January 2002 and December 2015 at the Pregnant Women Critical Care Unit of Chaoyang Hospital, Capital Medical University, Beijing, China were retrieved. The rate of acute pancreatitis in preeclampsia/eclampsia patients was calculated and patients with preeclampsia/eclampsia and acute pancreatitis were included for further analysis. RESULTS: Totally 1703 pregnant women who received medical care at our institution during the review period were diagnosed with hypertension. Four hundred and seven (23.9%) of them had severe preeclampsia. Five (1.2%, 5/407) women with severe preeclampsia developed acute pancreatitis. Their median age was 32 (range 25-35) years and the median duration of gestation was 32 (range 28-40) weeks. Mild acute pancreatitis occurred in three cases, and moderately severe and severe acute pancreatitis in one case each. Four patients underwent cesarean resection and one patient underwent vaginal delivery. Conservative therapy was undertaken. No patient received surgical intervention and cure was achieved in all patients. CONCLUSION: Acute pancreatitis may complicate severe preeclampsia/eclampsia or may be concurrent with severe preeclampsia/eclampsia, complicating and compromising the management of preeclampsia/eclampsia. Physicians should be alert for the presence of acute pancreatitis as prompt diagnosis and treatment, rapid termination of pregnancy and subsequent conservative management of pancreatitis could lead to a general favorable outcome.

[Preeclampsia: New Classifications]. / Präeklampsie: neue Definitionen.

Preeclampsia: New Classifications Abstract. Preeclampsia is a multisystem disease leading to systemic impairment of the maternal endothelial function. A dysbalance of pro- and antiangiogenic factors appears to be significantly involved. The vascular disease leads to the manifestation of symptoms such as arterial hypertension and involvement of end organs such as kidney, liver and brain. The classical diagnostic criterion for arterial hypertension, 'proteinuria' has been downgraded and is no longer obligatory for diagnosis, if other criteria, as maternal organ dysfunction or intrauterine growth retardation, are present. In addition, white-coat hypertension has been included in the classification of hypertension in pregnancy. To classify preeclampsia as 'mild' is being discouraged in the clinical setting to account for the possibility of rapid worsening with significant danger for mother and foetus.