Development Of Preeclampsia In Women Research Articles

Analysis of ICAM-1 rs3093030, VCAM-1 rs3783605, and E-Selectin rs1805193 Polymorphisms in African Women Living with HIV and Preeclampsia.

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.

Glycemic control assessed by continuous glucose monitoring during pregnancy in women with type 1 diabetes and its association with preeclampsia, an observational Swedish cohort study.

Women with type 1 diabetes have an increased risk of preeclampsia (PE), but it is not fully understood if degree of glycemic control is associated with this risk. The aim of this study was to assess glycemic control during pregnancy analyzed by continuous glucose monitoring (CGM) in women with and without PE and to investigate if glycemic control is associated with increased risk of PE. A total of 120 pregnant Swedish women with type 1 diabetes using CGM were included. Background factors and pregnancy outcomes were collected from medical records. CGM data were collected via the internet-based platform Diasend. Mean glucose, standard deviation of mean glucose, percentage of time in target, time below target, and time above target were presented for each trimester in women who did or did not develop PE. Associations between CGM-derived metrics and PE were analyzed with logistic regression and adjusted for confounders. Twenty-two women (18.3%) developed PE. There were no significant differences in maternal characteristics between women with and without PE. Glycemic control improved in each trimester but was suboptimal in both groups. Time in target increased from 59% in the non-PE group and 54% in the PE group in the first trimester to 65% in both groups in the third trimester. There were no significant associations between glycemic control and PE after adjustment for confounders. Degree of glycemic control during pregnancy assessed by CGM was not associated with development of PE in women with type 1 diabetes. However, more research is needed to understand the role of glycemic control in relation to development of PE.

Аналіз перинатальних наслідків у жінок із загрозою невиношування вагітності в першому триместрі залежно від факту утворення ретрохоріальної гематоми

Purpose - to evaluate the effectiveness of the developed personalized approach to the management of patients with a threat of miscarriage in the first trimester depending on the fact of the formation of a retrochorial hematoma (RCH) in order to prevent the occurrence of preeclampsia (PE) in them. Materials and methods. A prospective analysis of the course of pregnancy and childbirth was conducted in 137 women with a threat of pregnancy aged from 20 to 47 years (the Group I - 60 patients with RCH, the Group II - 77 patients with a threat of termination of pregnancy without hematoma). Bibliosemantic analysis was used in the study; estimated anthropometric data; an enzyme-linked immunosorbent assay was performed to study hormone levels; polymerase chain reaction was used to determine polymorphisms of thrombophilia and angiogenesis genes; instrumental - to assess the condition of the fetus (ultrasound diagnosis of the fetus with Doppler blood flow of the umbilical artery, uterine arteries, middle cerebral arteries, non-stress test). Results. The average age of women of the Group I was 31.2±0.6 (95% CI: 30.0-32.4) years, of the Group II - 32.2±0.6 (95% CI: 31.0-33.3) of the year (p=0.243 according to the t-criterion). According to the Alberta Perinatal Health Program (APHP) adapted perinatal risk scale, 21 (35.0%) and 36 (46.7%) patients were assigned to the low perinatal risk group, respectively, and 30 (50.0%) medium risk) and 32 (41.5%) women, and to the high-risk group - 9 (15.0%) and 9 (11.7%) at p>0.05. During the treatment and observation of women with a threat of miscarriage in the first trimester, the developed treatment algorithm was followed: stabilization of the hematoma, reduction of myometrial tone, hormonal support of pregnancy with further determination of the need for the use, dose and duration of low-molecular-weight heparin (LMWH) in combination with aspirin. Differences between the Groups I and II revealed by means of a comparative analysis made it possible to outline the clinical and anamnestic factors that can serve as predictors of the development of PE in women with RCH. Conclusions. The occurrence of RCH at the stage of early placentation increases the risks of developing placental dysfunction and obstetric complications related to it. The early appointment of aspirin (up to 12 weeks) in women with a high risk of developing PE allows to reduce the synthesis of platelets and thromboxane while preserving the synthesis of prostacyclin in the vascular wall in the initial stages of placentation. The combination of aspirin with the use of LMWH in women with the presence of genetic polymorphisms of candidate genes for thrombophilia and angiogenesis prevents the delay in the onset of uteroplacental circulation and promotes full placentation. A personalised approach to the management of pregnancy in women with a threat of termination due to the formation of RCH in the first trimester of pregnancy has made it possible to improve perinatal outcomes in the management of this category of pregnant women. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Mediators of inflammation resolution and vasoactive eicosanoids in gestational diabetes and preeclampsia.

Women with gestational diabetes (GDM) have an increased risk of preeclampsia and postpartum diabetes. Inflammation associates with both GDM and preeclampsia. This study examined specialized proresolving mediators (SPM) that direct inflammation resolution and eicosanoids that are involved in inflammation, in relation to the development of preeclampsia and ongoing postpartum glucose intolerance in GDM. Participants were selected from a prospective study examining the development of preeclampsia in women with GDM. Four groups of age-matched women were studied: GDM ( n = 20), GDM who developed preeclampsia (GDM+PE, n = 21), GDM who remained glucose-intolerant postpartum (GDM+PPIGT, n = 20), or pregnancies with glucose tolerance within the normal range (NGT, n = 21). Measurement of SPM (E-series resolvins and D-series resolvins), SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA), 20-hydroxyeicosatetraenoic acid (20-HETE), and the urinary metabolite of the vasodilator prostacyclin 2,3-dinor-6-Keto-PGF 1α , were made at 28, 32 and 36 weeks gestation and at 6 months postpartum. Compared with GDM, GDM+PE had elevated levels of 20-HETE and the SPM pathway intermediates 14-HDHA, 18-HEPE, 17-HDHA, at 32 weeks, and the SPM RvE1 at 32 and 36 weeks gestation. Compared with NGT and regardless of whether they developed preeclampsia or PPIGT, GDM had lower levels of 2,3-dinor-6-Keto-PGF 1α during pregnancy. Reduced levels of the prostacyclin metabolite 2,3-dinor-6-Keto-PGF 1α may contribute to the increased risk of preeclampsia in women with GDM. The increase in 20-HETE, a vasoconstrictor and mediator of inflammation, and SPM that contribute to inflammation resolution, prior to the onset of preeclampsia require further investigation to clarify their clinical significance.

Hypothyroidism and the increased risk of preeclampsia – interpretative factors?

ABSTRACT Objective To evaluate the causes behind the association between hypothyroidism and the risk of preeclampsia. Methods Checking of individual hospital and birth records from 149 levothyroxine users among 2,508 women in the preeclampsia case–control study (2002-2016). Results There were significant association between levothyroxine medication and preeclampsia (OR 1.48, 95th CI 1.06–2.07; p ≤ 0.022). The presence of comorbid diseases was associated with a significantly higher risk for the development of preeclampsia in women using levothyroxine. Conclusion Levothyroxine use during pregnancy was associated with 1.5-times higher risk for preeclampsia, but it is also linked to the other comorbid risk factors.

Prognostic Value of Maternal Cardiovascular Hemodynamics in Women With Gestational Hypertension and Chronic Hypertension in Pregnancy

This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George's Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and systemic vascular resistance (SVR) and weight-adjusted indices. The primary outcome was the time to development of preeclampsia in women with gestational hypertension or chronic hypertension. In women with gestational hypertension or chronic hypertension (n=149), cox-proportional hazards analysis showed that mean arterial pressure (P=0.006), Afro-Caribbean ethnicity (P=0.045), and gestational age at the time of diagnosis above 34 weeks (P<0.001) were significantly associated with increased risk of earlier preeclampsia. Women with high SVR and normal CO (adjusted hazard ratio, 2.32 [95% CI, 1.06-5.08]; P=0.035) and high SVR and low CO (adjusted hazard ratio, 7.79 [95% CI, 1.94-31.24]; P=0.003) cardiovascular profiles had significantly higher risk of earlier preeclampsia compared with women with normal SVR and normal CO. The findings of this study demonstrate that hypertensive women with increased SVR and low CO had a higher risk of developing preeclampsia sooner.

Elevated Early Third Trimester Hemoglobin as a Predictor of Preeclampsia [14L

INTRODUCTION: One of the early physiologic changes in pre-eclampsia (PE) is increased vascular permeability that can cause hemoconcentration. We hypothesized higher hemoglobin (Hgb) may be an early marker for development of PE. METHODS: During a 3 year period, records of women without known renal disease and a gestational age at delivery (GAD) &gt;24 weeks were evaluated. PE was defined as elevated blood pressure (&gt;140/90) and increased protein: creatinine ratio (PCR&gt;0.29). The Hgb obtained between GA 22-32 weeks were reviewed. In addition to GAD, maternal age (MA) and body mass index (BMI) was recorded. Odds ratios (OR, 95% CI) were determined for the development of PE in women with Hgb &gt;12.9 and &gt;13.9 grams. RESULTS: Of the 10,418 deliveries, 901 (8.6%) were diagnosed with PE. Women with PE delivered earlier (37.2 ± 2.8 vs 38.6 ± 2.1 wks, P&lt;.001) and had higher BMI (35.2 ± 7.1 vs 32.6 ± 6.2 Kg/M2, P&lt;.001). Of the 396 women with a Hgb &gt;12.9, 74 developed PE (OR 2.5, 1.8-3.1, P&lt;.001). Other than GAD (34.4±5.5 vs 37.2±3.6 wks, P&lt;.001), PE with Hgb&gt;12.9 did not differ in MA or BMI. Of 44 women who had Hgb&gt;13.9, 14 developed PE (OR 4.7, 2.5-8.9, P&lt;.001). PE with Hgb&gt;13.9 did not differ in GAD, MA or BMI, however sample size was limited. CONCLUSION: In this retrospective case control study, elevated Hgb was associated with PE. Most pregnant women have Hgb between 24 to 30 weeks. This inexpensive, ubiquitous test may provide an additional warning sign for the development of PE.

A model for predicting the risk of preeclampsia in women with different somatotypes

Hypothesis/aims of study. Preeclampsia is a serious pregnancy-specific multi-organ disease of complex etiology. It affects 36% of expectant mothers worldwide and it persists as a leading cause of maternal and fetal morbidity and mortality. This study aimed at analyzing the frequency of preeclampsia in women with different somatotypes and at developing a prediction model to determine the risk of this disease.&#x0D; Study design, materials and methods. 390 women were examined, of whom 110 were of the macrosomatic type, 173 of the mesosomatic type, and 107 of the microsomatic type. Somatometry was performed according to R.N. Dorokhov in women in early pregnancy (before 910 weeks of gestation). The urinary excretion of markers for podocyte injury (nephrin, podocalyxin, and VEGF) was measured using ELISA spectrophotometric methods.&#x0D; Results. Preeclampsia has been found to be significantly more prevalent among the representatives of the macrosomatic type, compared to women of the meso- and microsomatic types. Urine nephrin, podocalyxin and VEGF levels were significantly higher in women of the macrosomatic type, as compared to those of the meso- and microsomatic types. Using multiple regression analysis, we obtained the regression equation (formula), which predicts the development of preeclampsia in women of different somatotypes.&#x0D; Conclusion. Carrying out calculations according to the presented formula allows predicting the occurrence of preeclampsia with high accuracy, as well as forming high-risk groups among patients already in the first trimester of pregnancy when a pregnant woman is registered in the womens consultation, long before the disease develops. This will contribute to more effective implementation of therapeutic measures to prevent the development of this complication.

Physical activity, sedentary behavior and development of preeclampsia in women with preexisting diabetes.

To explore the association between physical activity in early pregnancy and development of preeclampsia in women with preexisting diabetes. In a prospective cohort study of 189 women with preexisting diabetes (110 type 1 and 79 type 2 diabetes), physical activity during pregnancy including sedentary behavior was evaluated with the Pregnancy Physical Activity Questionnaire. Primary outcome was preeclampsia. Secondary outcomes were preterm delivery, large and small for gestational age infants. Women developing preeclampsia (n = 23) had higher diastolic blood pressure in early pregnancy (mean 82 ± 9 SD vs. 77 ± 8, p = 0.004) and were more often nulliparous (91 vs. 52%, p < 0.001) compared with the remaining women (n = 166). Total physical activity in early pregnancy was similar between the groups (median 148 metabolic equivalent of task hours per week (MET-h/week) (interquartile range 118-227) versus 153 (121-205), p = 0.97). In early pregnancy, women developing preeclampsia reported a higher level of sedentary behavior (15 MET-h/week (7-18) versus 7 (4-15); p = 0.04); however, when adjusting for parity, diastolic blood pressure and smoking, the association attenuated (p = 0.13). Total physical activity and sedentary behavior in early pregnancy were not associated with preterm delivery, large or small for gestational age infants. Among women with diabetes, sedentary behavior was reported higher in early pregnancy in women developing preeclampsia compared with the remaining women, while total physical activity was similar. Sedentary behavior was a predictor of preeclampsia in the univariate analysis, but not in the multiple regression analysis, and larger studies are needed to evaluate this possible modifiable risk factor. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT02890836).

Prepregnancy and Early Pregnancy Calcium Supplementation Among Women at High Risk of Preeclampsia: A Multicenter, Double-blind, Randomized, Placebo-controlled Trial

(Lancet. 2019;393:330–339) Approximately 14% of maternal deaths worldwide are directly caused by hypertensive disorders of pregnancy, including preeclampsia. On the basis of surprisingly low rates of preeclampsia in low-income countries with high-calcium diets, it has been suggested that calcium deficiency may be linked to preeclampsia and several randomized controlled trials (RCTs) have tested the hypothesis that calcium supplementation may prevent preeclampsia. One study found reductions in the severity of preeclampsia, maternal morbidity and mortality and neonatal mortality, but no significant effect on preeclampsia prevalence. A meta-analysis of 13 RCTs found that calcium supplementation decreased preeclampsia rates by approximately half, but one limitation was small sample sizes of the studies included. This current study aimed to determine whether calcium supplementation before pregnancy and during the first half of pregnancy would reduce the development of preeclampsia in women who experienced preeclampsia or eclampsia in a previous pregnancy.

PKC Modulates sFlt1 Production by Human Placental Trophoblasts in Response to Oxidized LDL

Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and mortality, and its prevalence is 4 fold higher in women with diabetes than those without: the underlying mechanism is unclear. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) plays a key role in PE pathogenesis. Evidence suggests that PKC activation, which is associated with the development of diabetic vascular complications, may mediate the enhanced sFlt1 release in non-trophoblast cells. We aimed to determine the role of PKC in the regulation of sFlt1 expression in placental trophoblasts, and whether diabetic conditions upregulate sFlt1 expression via the PKC pathway. Human trophoblasts HTR8/SVneo were treated in three separate experiments with PKC activator phorbol-12-myristate-13-acetate (PMA), or diabetes stimuli ’heavily oxidized, glycated’ low-density lipoproteins (HOG-LDL) vs. native LDL ± high glucose (30 mM), over 24h, with or without PKC inhibitor GF109203X (GX). Both sFlt1 mRNA expression (RT-PCR) and protein release (ELISA) were measured. Compared to the control, PMA (5 nM) increased sFlt1 mRNA expression (2.5 fold, p&amp;lt;0.001) and protein release (383.8 ± 27.4 vs. 118.3 ± 21.3 pg/ml, p&amp;lt;0.001) in trophoblasts; these effects were entirely abrogated by the pre-treatment with 5 uM GX for mRNA expression (by 54%, p&amp;lt;0.001) and protein release (115.5 ± 20.9 pg/ml, p&amp;lt;0.001) vs. PMA-treated cells. Similarly, HOG-LDL (50 µg/ml) increased sFlt1 mRNA expression (3.7 fold, p&amp;lt;0.001) and protein release (126.4 ± 16.3 vs. 55.1 ± 2.4 pg/ml, p&amp;lt;0.001), and the both effects were partially abolished by GX (by 33-37%, p&amp;lt;0.05). High glucose did not significantly affect sFlt1 expression, or alter the effect of HOG-LDL. The data suggest that modified lipoproteins may promote PE development in women with diabetes, at least in part via PKC-mediated upregulation and release of sFlt1. These findings provide new insights into disease mechanisms, and may lead to new targets for prevention and treatment of PE. Disclosure R.P. Chow: None. J. Zhao: None. J. Yu: None.

Diabetes and Pregnancy

Diabetes and Pregnancy

Hypertension: Testing for pre-eclampsia: paving the way to early diagnosis.

A new study reports that a single blood test can be used to rule out the development of pre-eclampsia in women in whom the syndrome is suspected. Early interventions for pre-eclampsia are not yet available, but this finding is likely to change the approach to diagnosis of hypertensive disorders in pregnancy.

Genetic markers for prediction of early and late onset preeclampsia in pregnant women with preexisting type 1 diabetes mellitus

The study compared the profile of polymorphic variants of genes that determine the basic pathogenesis of pre-eclampsia in groups of patients with type 1 diabetes. Overall, 60 female patients with type 1 diabetes were investigated: pregnancy complicated with early-onset (n = 15) and late-onset (n = 15) superimposed preeclampsia was reported in 30 subjects; no complications were detected among the rest 30 patients. Besides standard clinical investigation, each patient underwent molecular genetic testing with detection of the following polymorphic variants of genes: А1166С-AT2R1, C108T-PON1, Thr83Ala- and T138C-MGP, 4b/4a- and G894T-eNOS, as well as I/D-ACE.On completion of our study we established differential prognostic models for prediction of early-and late-onset preeclampsia development in women with pre-existing type 1 diabetes mellitus based on the data about the prevalence of polymorphic variants of genes and gene-gene interactions.The following risk factors were found to be the main contributors to early-onset (&lt; 32 weeks) preeclampsia development: long duration of diabetes; presence of vascular complications at the time of conception (in particular, diabetic angiopathy of lower extremities and diabetic nephropathy); and ACE ID-genotype. The most significant genotype combinations associated with early-onset preeclampsia development were as follows: ACE (ID) / AT2R1 (1166АА), ACE (ID) / AT2R1 (1166АС), ACE (I/D) / eNOS (4b/4b), ACE (I/D) / eNOS (894GG). Genetic factor influenced the development of late-onset preeclampsia (≥ 32 weeks) to a much lesser extent; only one statistically significant combination of genotypes was detected to be associated with preeclampsia debut after 32 weeks of pregnancy – ACE (ID) / MGP (138TC). Genotype combination ACE (II) / PON1 (108CC) significantly reduced the risk of preeclampsia development during the entire pregnancy.Important genetic markers found in our study will allow predicting different forms of preeclampsia in type 1 diabetic pregnant women. Identification of women at high risk for early-onset preeclampsia development will let us to implement treatment and preventive measures and to provide closer monitoring, resulting in better pregnancy outcomes.

First-Trimester Risk Factors for Preeclampsia Development in Women Initiating Aspirin by 16 Weeks of Gestation

The residual risk of preeclampsia in high-risk women on aspirin prophylaxis exceeds that of low-risk populations, and this study aimed to identify first-trimester maternal characteristics associated with aspirin prophylaxis failure. This is a nested cohort study of prospectively enrolled women with verified initiation of risk-indicated aspirin prophylaxis by 16 weeks of gestation. First-trimester maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women who developed preeclampsia and those who did not. Blood pressure measurements were classified as prehypertension or hypertension according to the Joint National Committee on Hypertension guidelines. Chi square, nonparametric, and logistic regression analyses were used to determine the contributors to preeclampsia development. Six hundred fourteen women prospectively enrolled at 9-14 weeks of gestation initiated aspirin by 16 weeks of gestation. The 59 (9.6%) women who developed preeclampsia were more likely to have chronic hypertension, diabetes, and obesity and had higher first-trimester blood pressure and lower serum pregnancy-associated plasma protein-A concentrations (all P<.05). Having first-trimester Joint National Committee on Hypertension prehypertension or hypertension was associated with a 2.18-fold increased risk of developing preeclampsia, whereas normotension was associated with a reduction of risk of 56%. Women who develop preeclampsia while taking aspirin prophylaxis are more likely to have elevated first-trimester blood pressures. Conversely, first-trimester normotension is associated with a reduced risk of preeclampsia.

Absence of Association Between Serum Folate and Preeclampsia in Women Exposed to Food Fortification

To evaluate serum folate concentration early in pregnancy and any association with hypertensive disorders of pregnancy in a population exposed to folic acid supplementation and food fortification. This is a nested case-control study based on a prospective cohort of 7,929 pregnant women recruited in the Quebec City metropolitan area, including 214 participants who developed a hypertensive disorder of pregnancy and 428 normotensive participants in the control group matched for parity, multiple pregnancy, smoking status, gestational, and maternal age at inclusion, and duration of blood sample storage. Serum folate levels were measured at a mean of 14 weeks of gestation. More than 98% of the participants took folic acid or multivitamins before the end of the first trimester. Mean serum folate levels were accordingly high and there were no differences between women who further developed a hypertensive disorder of pregnancy compared with women in the control group (60.1 nmol/L compared with 57.9 nmol/L; P=.51). The proportion of participants with serum folate below the 10th percentile (less than 22.3 nmol/L) of age-matched women in our outpatient population was similar between groups (P=.66) and no participant had levels generally defined as folate deficiency (less than 10 nmol/L). In a general cohort of pregnant women benefiting from a national policy of folic acid food fortification combined with a high adherence to folic acid supplementation, serum folate levels are high and do not differ between women who develop a hypertensive disorder of pregnancy and women who remain normotensive. Further supplementation with higher doses is unlikely to be beneficial in such populations. II.

Serum Inflammatory Markers and Preeclampsia in Type 1 Diabetes

OBJECTIVEInflammation and endothelial dysfunction have been associated with the immunobiology of preeclampsia (PE), a significant cause of adverse pregnancy outcomes. The prevalence of PE is elevated several fold in the presence of maternal type 1 diabetes mellitus (T1DM). Although cross-sectional studies of pregnancies among women without diabetes have shown altered inflammatory markers in the presence of PE, longitudinal studies of diabetic women are lacking. In maternal serum samples, we examined the temporal associations of markers of inflammation with the subsequent development of PE in women with T1DM.RESEARCH DESIGN AND METHODSWe conducted longitudinal analyses of serum C-reactive protein (CRP), adhesion molecules, and cytokines during the first (mean ± SD, 12.2 ± 1.9 weeks), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy (visits 1–3, respectively). All study visits took place before the onset of PE. Covariates were BMI, HbA1c, age of onset, duration of diabetes, and mean arterial pressure.RESULTSIn women with T1DM who developed PE versus those who remained normotensive, CRP tended to be higher at visits 1 (P = 0.07) and 2 (P = 0.06) and was significantly higher at visit 3 (P < 0.05); soluble E-selectin and interferon-γ–inducible protein-10 (IP-10) were significantly higher at visit 3; interleukin-1 receptor antagonist (IL-1ra) and eotaxin were higher and lower, respectively, at visit 2 (all P < 0.05). These conclusions persisted following adjustment for covariates.CONCLUSIONSIn pregnant women with T1DM, elevated CRP, soluble E-selectin, IL-1ra, and IP-10 and lower eotaxin were associated with subsequent PE. The role of inflammatory factors as markers and potential mechanisms of the high prevalence of PE in T1DM merits further investigation.

Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Antenatal clinics. Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Maternal serum levels of sRAGE (total circulating pool), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.

PP173. The role of mean artery blood pressure in the prediction of pre-eclampsia in pregnancies complicated with chronic hypertension

Chronic hypertension (CH) is a common disorder occurring in approximately 1-5% of pregnant women. Many studies emphasize that the development of superimposed preeclampsia (PE) is associated with high rates of adverse pregnancy outcome. Accurate prediction of women at risk for PE is crucial to judicious allocation of monitoring resources and use of preventive treatment, in order to improve maternal and neonatal outcome. Recent systematic review and meta-analysis showed that mean arterial pressure (MAP) is a better predictor for pre-eclampsia than systolic blood pressure and diastolic blood pressure To detect the value of MAP in the first and second trimesters to predict PE in women with CH. To determine if MAP, assessed in the second trimester, can increase the predictive value for PE of II trimester UtA PI. Cohort study on 100 consecutive singleton pregnancies complicated with CH referred to our Department from January 2008 to June 2011. Blood pressure was measured by a mercury sphygmomanometer at 11-14+6w and 23+0-25+6w, MAP was calculated. Doppler-velocimetry was performed at 23+0-25+6w, mean UtA PI was calculated. PE and CH were defined according to ISSHP criteria. Clinical and perinatal outcomes were reviewed. Receiver-operating characteristic (ROC) curves were used to determine the predictive ability of I and II trimesters MAP and II trimester mean UtA PI for subsequent development of PE. Logistic regression analysis was run to assess the additional value of II trimester MAP to II trimester UtA PI. Mean maternal age was 36 years (SD ±5yy); mean Body mass Index was 24Kg/mq (SD ±5Kg/mq); GA at I Trimester evaluation was 11+4w (SD ±1+5w); I trimester MAP was 100.46mmHg (mean, SD ±9.94mmHg); GA at Doppler and II trimester MAP was 24+4w (SD ±4dd); II trimester MAP 97.53mmHg (mean, SD ±10.27mmHg). Nineteen cases of PE were observed. Seventy patients were under prophylactic ASA 100mg oid. Fifty-two patients were under anti-hypertensive therapy from the first trimester. No differences in prevalence of PE were observed between patients in and out prophylactic treatment, as well as no differences in prevalence of PE were observed between patients under anti-hypertensive treatment or not. The prediction of subsequent development of PE, expressed as the area under ROC curve, was 0.469 (95% CI 0.34-0.59) for I trimester MAP; 0.659 (95% CI 0.55-0.76) for II trimester MAP; 0.748 (95% CI 0.65-0.83) for II trimester mean UtA PI; GA at delivery was 37+4w(mean, SD ±3+2w); mean BW was 2958g (SD ±735g); BW percentile was 38 (mean SD ±29 percentiles); mean BW z-Score was -0.63 (SD ±1.6). Logistic regression analysis showed that MAP does not increase the predictive ability of II trimester UtA PI in women with CH. In our findings, MAP seems not to be a good predictor for subsequent development of PE in women with CH, moreover, it seems to be not useful to increase the predictive value for PE of II trimester UtA PI. II trimester UtA PI has been confirmed to be the best predictor for subsequent development of PE.

A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes

The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. This was an observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c), blood pressure and urinary albumin excretion were recorded. Pre-eclampsia was defined as blood pressure >140/90 mmHg and proteinuria ≥300 mg/24 h after 20 weeks. Pre-eclampsia developed in nine women (8%) with longer diabetes duration (median 20 [range 10-32] vs 16 [range 1-36] years, p = 0.04), higher SSAO concentrations (592 [range 372-914] vs 522 [range 264-872] mU/l, p = 0.04) and a tendency towards higher prorenin levels (136 [range 50-296] vs 101 [range 21-316] ng angiotensin I ml(-1) h(-1), p = 0.06) at 8 weeks compared with women without pre-eclampsia. Levels of renin, angiotensinogen and ACE did not differ in the two groups. Throughout pregnancy, prorenin and SSAO levels were 30% (p = 0.004) and 16% (p = 0.04) higher, respectively, in women developing pre-eclampsia. Using multivariate logistic regression analysis, prorenin concentration at 8 weeks was associated with pre-eclampsia (OR 4.4 [95% CI 1.5-13.0], p = 0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher levels of prorenin and SSAO throughout pregnancy were seen.