Evaluation of maternal serum progranulin levels in normotensive pregnancies,and pregnancies with early- and late-onset preeclampsia

Aims: To investigate the possible pathophysiological associations between progranulin (PGRN) and preeclampsia (PE), early-onset PE (EOPE) and late-onset PE (LOPE).

Study design: A cross-sectional study was designed to include consecutive patients with uncomplicated pregnancy (n?=?28), EOPE (n?=?30) and LOPE (n?=?22). Maternal levels of serum PGRN were measured with the use of an enzyme-linked immunosorbent assay kit.

Results: The mean serum PGRN level was significantly higher in women with PE compared to the control group (54.17?±?4.20?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001), in the LOPE group compared to the control group (51.63?±?4.61?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001) and also in women with EOPE compared to women with LOPE (56.03?±?2.68?pg/ml versus 51.63?±?4.61?pg/ml, p?<?0.001). Serum PGRN was negatively correlated with gestational age at birth (r?= ?0.669, p?=?0.001) and birth weight (r?= ?0.653, p?=?0.001); and positively correlated with systolic (r?=?0.653, p?=?0.001) and diastolic blood pressure (r?=?0.601, p?=?0.001), C-reactive protein (r?=?0.519, p?=?0.001), uterine artery pulsatility (r?=?0.441, p?=?0.001) and resistance indices (r?=?0.441, p?=?0.001).

Conclusions: Serum PGRN levels increase significantly in women with PE as an indirect sign of placental dysfunction. This increase is even more prominent in women with EOPE. The serum PGRN in the third trimester is positively correlated with gestational age at birth and birth weight.     

Lower circulation levels and activity of α-1 Antitrypsin in pregnant women with severe preeclampsia

Objective: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5?mg/dl and rise during pregnancy. Although AAT deficiency is associated with several pregnancy and placental disorders, little is known regarding AAT levels and preeclampsia. Since unopposed inflammation might contribute to preeclampsia, we studied whether preeclampsia is associated with lower than normal levels and activity of AAT. Methods: In a prospective case-control study, we compared maternal serum AAT activity and levels between patients with severe preeclampsia (n = 23) and without preeclampsia (n = 18). Results: AAT levels were 1.91?±?0.08-fold lower in the preeclampsia group compared to healthy group (3.854?±?0.26 vs. 7.397?±?0.34?mg/ml; p < 0.001), and correlated with protease inhibitory capacity (46.56?±?2.08% vs. 67.08?±?1.74%; p < 0.001). Conclusions: Our findings show association between lower AAT levels and severe preeclampsia during pregnancy. Further studies are required to identify the mechanism behind the association, and the possibility of safe AAT augmentation for individuals with insufficient circulating AAT.     

The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia

Aim: To investigate the biochemical and genetic thyroid status in women with preeclampsia by the determination of serum FT3 and FT4 levels in association with D1-C785T genotypes. Methods: We genotyped using PCR–RFLP methods 50 women with preeclampsia and 50 normotensive pregnant women. Results: FT3 levels (pg/ml, 2.63?±?0.56 vs. 2.91?±?1.41) were low, and FT4 levels (ng/dl, 1.11?±?0.3 vs. 0.88?±?0.14) were high in women with preeclampsia compared to normal pregnant women. The association with severe preeclampsia was stronger for the homozygous T/T genotype (OR 6.57, p?=?0.029). Women with preeclampsia with the D1-T785 mutated allele had lower FT3 levels (pg/ml, 2.31?±?0.81 vs. 3.04?±?0.39, p?<?0.001), higher FT4 levels (ng/dl, 1.32?±?0.87 vs. 0.84?±?0.24, p?=?0.009) than women with preeclampsia with the D1-C/C genotype. Significant decrease in serum FT3 levels in positive women with severe preeclampsia compared to women negative for this genetic variation (pg/ml, 1.59?±?0.74 vs. 2.77?±?0.23, p?=?0.003) was observed. Women with severe preeclampsia, positive for the mutated T785 allele, delivered at a significantly lower gestational age (31.75?±?3.69 vs. 38.66?±?3.21 weeks, p?=?0.035) neonates with a lower birth weight (1861.11?±?869.9 vs. 3500?±?424.26?g, p?=?0.023) compared to women negative for the same allele. Conclusions: Thyroid hormone levels and the D1-C785T polymorphism, alone or in combination, correlate with the severity of preeclampsia. The D1-C785T polymorphism influences the outcome of pregnancy in severe preeclampsia.     

Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders

Objectives: The utility of angiogenic and antiangiogenic biomarkers as diagnostic tools in preeclampsia (PE) has been shown in previous studies. Our study’s aim was to evaluate the use of automated measurement of sFlt1, PlGF and their ratio (sFlt1/PlGF) in differential diagnosis of hypertensive pregnancy disorders. Patients/Methods: Sixty-four patients with PE/HELLP, 18 with pregnancy-induced hypertension (PIH), 22 with gestational proteinuria (GP) and 232 controls were investigated. The PE/HELLP group was divided into mild PE (mPE, n?=?31), severe PE (sevPE, n?=?20), superimposed PE (supPE, n?=?7) and HELLP syndrome (n?=?6). sFlt1 and PlGF were measured in serum samples on an automated platform. Statistical analysis was performed using parametric and non-parametric methods, ROC analysis and logistic regression method. Results: PE patients showed higher sFlt1 and ratio and lower PlGF than controls (median?±?SEM in pg/mL; 10?888?±?878 versus 2456?±?116; 268?±?39 versus 16?±?2 and 68?±?6 versus 439?±?37, each p?<?0.001), subgroups showed similar differences in ratios (median?±?SEM; supPE: 202?±?110; mPE: 137?±?27; sevPE: 497?±?91; HELLP syndrome: 254?±?72 versus controls 16?±?2, each p?<?0.001). ROC analysis showed best performance for sFlt1/PlGF (AUC all PE: ratio 96.4%, sFlt1 92.8%, PlGF 92.4%, supPE: ratio 93.6%, mPE: ratio 94.8%, sevPE: ratio 99.4%, HELLP: ratio 98.6%, each versus controls). Patients with PIH and GP showed significant differences compared to controls (p?≤?0.01, respectively), mPE (p?≤?0.007), sevPE (p?<?0.001) and HELLP syndrome (p?≤?0.003). Conclusion: The automated measurement of sFlt1/PlGF is a reliable diagnostic tool in differential diagnosis of hypertensive pregnancy disorders and gives additional valuable information for clinical management.     

Impairment of thiol-disulfide homeostasis in preeclampsia

Aim: To investigate the effects of severity of preeclampsia on thiol-disulfide homeostasis (TDH).

Material and methods: A total of 108 participants were divided into three groups: Group 1 was composed of pregnant women with no obstetric complications, Group 2 included pregnant women with mild preeclampsia, and Group 3 consisted of pregnant women with severe preeclampsia. TDH parameters were determined, and comparisons of clinical and routine laboratory test findings were made in all groups.

Results: The serum native thiol level was 347.9?±?27.4 in the control group, 237.2?±?44.2 in the mild preeclampsia group, and 227.9?±?53.1 in the severe preeclampsia group (p?<?0.001). The serum total thiol level was 376.1?±?31.9 in the control group, 261.8?±?49.4 in the mild preeclampsia group, and 248.3 ± 57.4 in the severe preeclampsia group (p?<?0.001). The disulfide level was 14.1?±?5.6 in the control group, 12.3?±?5.1 in the mild preeclampsia group, and 10.2?±?4.8 in the severe preeclampsia group (p?=?0.001). A significant correlation between impairment in degree of TDH and severity of preeclampsia was observed.

Conclusion: TDH was impaired in women with preeclampsia, and this impairment increased with disease severity. Therefore, impaired TDH may have a role in the etiopathogenesis of the disease.     

Perinatal outcome for pregnancies complicated with thrombocytopenia

Introduction: Thrombocytopenia affects about 10% of all pregnancies. Preeclampsia/HELLP syndrome induced thrombocytopenia may associate perinatal morbidity, preterm delivery, or low-birth-weight newborns. Objective: To assess perinatal outcome and complications of pregnancy in women presenting with thrombocytopenia. Methods: We retrospectively analyzed 936 consecutive pregnant women admitted during a 6-month period. Results: Incidence of thrombocytopenia in pregnancy was 11.11% (104/936). Thrombocytopenia represented a risk factor for premature delivery – highest risk for severe thrombocytopenia (RR?=?8.69, p?<?0.01). Thrombocytopenic preeclampsia or HELLP syndrome associated the highest rates of prematurity (RR?=?7.97, p?=?0.00, respectively 12.32). Thrombocytopenia also represented a risk factor for low-birth-weight newborns, especially severe thrombocytopenia – 2047.50?±?938.98?g (p?=?0.02) versus 3224.86?±?496.00?g in controls. Again, thrombocytopenic preeclampsia was significantly associated with low-birth-weight newborns (RR?=?11.94, p?=?0.00), with medium weight of 2462.05?±?794.54?g versus 2932.37?±?708.91?g in thrombocytopenic pregnancies, respectively 3224.86?±?496.00?g (p?=?0.00) in normal pregnancies. Conclusions: Thrombocytopenia in pregnancy was associated with perinatal morbidity, with the strongest association for preeclampsia and HELLP syndrome – for both prematurity and low-birth-weight: the lower the platelet count, the higher the risks for the fetus/newborn. Therefore, we strongly recommend close surveillance of thrombocytopenic mothers and their babies, in order to establish the etiology and the best moment for intervention.     

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby

Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51?±?0.14; 0.52?±?0.13; 0.58?±?0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40?±?0.10, p?=?0.005 1st trim; 0.42?±?0.10, p?=?0.007 2nd trim; 0.45?±?0.10, p?=?0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58?±?0.10; 0.63?±?0.14; 0.68?±?0.11), the difference was statistically significant only in the 2nd trimester (p?=?0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.     

P-wave and QT dispersion in hypertensive disorders of pregnancy

Abstract

Aim: To compare P-wave and QT dispersion values in hypertensive disorders of pregnancy and controls and also in preeclampsia, chronic hypertension, and gestational hypertension separately.

Material and methods: We included 140 hypertensive pregnants and 110 healthy age-matched pregnants in this study. The hypertensive pregnants were divided into three subgroups: preeclampsia (n?=?43), chronic hypertension (n?=?51), and gestational hypertension (n?=?46). P-wave and QT dispersion values were compared between groups.

Results: Hypertensive pregnants had higher P-wave (41.74?±?5.51 vs. 37.73?±?5.62, p?<?.001) and QTc dispersion (45.44?±?7.62 vs. 39.77?±?8.34, p?<?.001) values. In subgroup analysis, P-wave dispersion and QTc dispersion were different between preeclamptic, chronic hypertensive, and gestational hypertensive patients. Also, they were significantly higher in chronic hypertension as compared to gestational hypertension and they were higher in preeclampsia than in gestational hypertension. No difference was found according to these parameters between preeclampsia and chronic hypertension. In correlation analysis, both P-wave dispersion and QTc dispersion were positively correlated with systolic (r?=?0.409, p?<?.001 and r?=?0.306, p?<?.001) and diastolic blood pressure (r?=?0.390, p?<?.001 and r?=?0.287, p?<?.001) which are main clinical determinants of hypertensive disorders.

Conclusion: In clinical practice, chronic hypertensive pregnants are generally followed up in their future life for cardiovascular disorders. Also, we recommend that we must inform and follow preeclamptic patients for future cardiovascular diseases.     

Tenascin C levels in patients with mild and severe preeclampsia

Objective: To determine the serum tenascin-C (TN-C) levels in cases with mild and severe preeclampsia.

Methods: Pregnant women were divided into three groups, namely healthy pregnants (Group 1, n?=?20), pregnants with mild preeclampsia (Group 2, n?=?20) and pregnants with severe preeclampsia (Group 3, n?=?20). The groups were formed so as to match each other in terms of gestational week. From each pregnant woman, pre- and post-delivery blood samples were obtained to measure serum TN-C levels. The data were evaluated using the Kruskall–Wallis variance analysis. For the obtained values of p?<?0.05, the groups were compared in pairs. A p value of <?0.017 was accepted as significant.

Results: In Groups 1, 2 and 3, the prepartum TN-C levels were 5.02?±?0.4?µg/ml, 12.8?±?2.9?µg/ml and 33.8?±?11.7?µg/ml, and in the postpartum TN-C levels were 4.7?±?0.1?µg/ml, 11.7?±?1.8?µg/ml and 50.6?±?33.8?µg/ml, respectively. There was a significant difference between the groups in terms of the prepartum and postpartum TN-C levels (p?<?0.017, Mann–Whitney U [MWU] test). There was also a significant difference in the prepartum TN-C levels between Groups 2 and 3 (p?<?0.017, MWU test).

Conclusions: The prepartum and postpartum TN-C levels were significantly higher in mild and severe preeclampsia than those in healthy pregnants.     

Preeclampsia in women with chronic kidney disease

Objective: Women with chronic kidney disease have an increased risk of developing preeclampsia and its severe complications. Currently, there are no assessments available in order to quantify such risk. The aim of the study is to establish the incidence of superimposed preeclampsia in women with chronic kidney disease according to Serum creatinine (SCr) level. Methods: Pregnant women with chronic kidney disease were retrospectively identified from January 2000 to July 2010. We defined two groups according to SCr: Group 1: SCr ≤ 125 µmol/l; Group 2: SCr > 125 µmol/l. Incidence of preeclampsia, early preeclampsia (delivery <34 weeks), gestational age (GA) at diagnosis and delivery outcome were assessed. Results: Ninety-three nephropatic women were considered for the analysis. Group 2 (n?=?14) compared with Group 1 (n?=?79) had an increased incidence of preeclampsia (78.6% vs. 25.3%; p?<?0.0001), an increased rate of pregnancy complications as early preeclampsia (82% vs. 38%; p?<?0.03), a lower GA at diagnosis (29?±?2 vs. 33?±?1 weeks; p?<?0.04) and a lower GA at delivery (30?±?2 weeks vs. 34?±?1; p?<?0.04). Conclusion: Women with chronic kidney disease and an increased creatinine threshold have a high risk of developing preeclampsia and delivering preterm.     

Maternal serum glycodelin levels in preeclampsia and its relationship with the severity of the disease

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.

Methods: This is a prospective case–control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.

Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38?±?22.78 versus 42.32?±?12.28?ng/ml, p?p?r?=?0.637 and r?=?0.714, respectively, p?r?=?0.369, p?=?.006 and r?=?0.377, p?=?.005) and proteinuria (r?=?0.342, p?=?.011). Moreover, it was correlated with birth weights and gestational age at delivery (r?=??0.386, p?=?.004 and r?=??0.394, p?=?.003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p?53.64?ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p?83.97?ng/ml.

Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia.     

Clinical trial of expectant management of severe preeclampsia that develops at <32 weeks’ gestation at a Japanese perinatal center

Abstract

Objective: This study was to examine the clinical usefulness of expectant management of early-onset severe preeclampsia.

Methods: We reviewed the obstetric records of all Japanese singleton deliveries at ≥22 weeks’ gestation managed at Japanese Red Cross Katsushika Maternity Hospital between 2007 and 2012. We compared the obstetric characteristics and perinatal outcomes between the cases of deliveries before (n?=?19) and after completion of corticosteroids (n?=?30) (immediate delivery versus expectant management).

Results: Although the gestational age at delivery in the patients expectantly managed was higher than that in the patients required immediate deliveries (31.0 versus 29.3 weeks), the difference in the incidence of neonatal respiratory distress syndrome between the two groups did not reach the statistical significance (74 versus 47%, p?=?0.06). The incidence of pulmonary edema in the patients expectantly managed was significantly higher than that in the patients required immediate deliveries within the first 48?h (20 versus 0%, p?=?0.04).

Conclusion: The current results could not support the clinical usefulness of expectant management of early-onset severe preeclampsia.     

Hemodynamically-Directed Atenolol Therapy is Associated with a Blunted Rise in Maternal sFLT–1 Levels During Pregnancy

Objective: Cardiac output and sFlt-1 are elevated prior to clinical evidence of preeclampsia. Early treatment of high cardiac output with atenolol decreases the risk for preeclampsia. We hypothesized that atenolol would impact circulating sFlt-1. Methods: Cardiac output and plasma sFlt-1 were measured ≤24 weeks' gestation and every 6 to 8 weeks in a longitudinal pilot study of: 1) women with risk factors for preeeclampsia (high-risk group; n?=?46) who were treated with atenolol, and 2) low-risk group (control, n?=?25) who were not treated. Results: The groups were similar in maternal age (mean±SD: high-risk 28.3?±?5.4 versus control 30.3?±?5.5 years) and enrollment gestational age (17.3?±?4.3 versus 16.1?±?4.2 weeks). The high-risk group had higher cardiac output (9.7?±?1.7 versus 7.3?±?1.7 L/min; p?<?0.001) and mean arterial pressure (91.8?±?10.6 versus 79.6?±?7.3 mm Hg; p?<?0.001). Cardiac output and mean arterial pressure decreased while sFlt-1 levels rose less in the high-risk group compared with controls (p?=?0.001 for all using GEE) even after adjusting for preeclampsia risk factors (age, weight, and primigravida status). Conclusion: Atenolol in high-risk women was associated with a lower rise in sFlt-1, suggesting an effect of hemodynamically directed treatment on the anti-angiogenic state.     

Higher levels of thyrotropin in pregnancy and adverse pregnancy outcomes

Objective: To determine the frequency of subclinical hypothyroidism in women with pathological pregnancies and the association between elevated thyroid-stimulating hormone (TSH) and pregnancy outcome.

Subjects and methods: A cross-sectional prospective study investigated value of TSH and free thyroxine (FT4) in (1) pregnant women with hypertension (HTA) (N?=?62) or preeclampsia (PE) (N?=?50), (2) women with gestational diabetes mellitus (GDM) (N?=?92) in pregnancy, and (3) women with normal pregnancies (control) (N?=?201). The level of statistical significance was set at p?Results: Of the total 404 respondents, the highest incidence of subclinical hypothyroidism was in the group with preeclampsia 22%, followed HTA group 9.6%; GDM group 10.9% and in the control group 9% (p?p?3?mIU/L (p?=?.003). There were no differences in the average TSH value between GDM (1.93?±?1.03?mIU/L) and control group (p?=?.962).

Conclusions: Early detection and optimal treatment of thyroid dysfunction before and in the first trimester of pregnancy reduces the risk of adverse pregnancy outcomes.     

Serum free fatty acid levels in PCOS patients treated with glucophage,magnesium oxide and spironolactone

Abstract

To assess the effect of glucophage, magnesium oxide and spironolactone in altering free fatty acids (FFAs), 36 PCOS women were randomly divided into three groups. Group 1 (n?=?14) was treated with 500?mg glucophage po bid, group 2 (n?=?10) was treated with 400?mg magnesium oxide po bid and group 3 (n?=?12) was treated with 50?mg spironolactone po bid for 12 weeks. A glucose tolerance test with 75?g glucose load was performed before and after treatment, collecting blood at 0, 1 and 2?h for insulin, glucose, FFA and aldosterone. Amount of FFA before and after treatment were compared by repeated measure ANOVA and represented as area under the curve. FFA levels before treatment were 0.83?±?0.23, 0.77?±?0.15 and 0.85?±?0.28 and after treatment were 0.77?±?0.48, 0.71?±?0.18 and 0.66?±?0.25 for glucophage, magnesium oxide and spironolactone-treated patients, respectively. The FFA levels were unchanged in the groups treated with glucophage and magnesium oxide but were significantly (p?<?0.03) decreased in the group treated with spironolactone. Since FFAs are known to be involved in the development of insulin resistance, these results suggest that spironolactone may be useful for lowering insulin resistance in PCOS patients.     

Clinical features and outcome of pregnancy with SLE-associated thrombocytopenia

Objective: To analyze the course of maternal diseases and compare pregnancy outcomes in patients with systemic lupus erythematosus (SLE)-associated thrombocytopenia to patients without.

Methods: Medical charts of 77 pregnancies in 73 SLE patients were systematically reviewed. Patients were divided into two groups according to the presence or absence of thrombocytopenia. Patients who are new onset SLE during pregnancy were also been studied.

Result: Thrombocytopenia was found in 18 (23.3%) of the pregnancies. SLE patients with thrombocytopenia during pregnancy had higher percentage of disease flaring (11/18 versus 14/59, p?=?0.003) and SLE-Pregnancy Disease Activity Index (7.89?±?6.192 versus 2.41?±?3.3.89, p?=?0.001) compared to patients without. Also, patients with thrombocytopenia had a higher percentage of pulmonary, cardiac and multiple organ system involvement. There was a statistically significant difference in preeclampsia and early onset hypertensive disorder induced before 34 weeks as well as the rate of live birth less than 34 weeks (33.3% versus 6.8%, p?=?0.003 & 38.9% versus 13.6%, p?=?0.018 & 16.7% versus 1.7%, p?=?0.038). Patients with thrombocytopenia suffered from higher rate of pregnancy loss (22.2% versus 3.4%, p?=?0.024) and neonatal death (33.3% versus 1.7%, p?=?0.000). In our study there were 17 patients with new-onset of SLE during pregnancy. The hematological system manifestation occurred in all of them and there was a significant increase in the incidence of thrombocytopenia (n?=?12, 70.6%).

Conclusion: Thrombocytopenia in SLE during pregnancy indicates higher disease activity, severe organ damage, early onset preeclampsia and higher pregnancy loss.     

Effect of regular exercise on prevention of excessive weight gain in pregnancy: A randomised controlled trial

Objectives?To assess whether a 12-week supervised exercise-programme with an additional 30?min of moderate self-imposed physical activity on the non-supervised weekdays prevents excessive weight gain in pregnancy, as well as postpartum weight retention.

Methods?One hundred and five sedentary, nulliparous pregnant women with a mean age of 30.7?±?4.0 years and a pre-pregnancy body mass index of 23.8?±?4.3?kg/m² were randomised to either an exercise group (EG, n?=?52) or a control group (CG, n?=?53). The exercise programme consisted of 60?min supervised aerobic dance and strength training for 60?min, at least twice per week for a minimum of 12 weeks.

Results?Drop-out rates were 19% and 21% in the EG and CG, respectively. Fewer women in the EG than in the CG exceeded the Institute of Medicine recommendations; however, only EG participants who attended 24 exercise sessions (n?=?14) differed significantly from controls (p?=?0.006) with regard to weight gain during pregnancy (11.0?±?2.3 vs. 13.8?±?3.8?kg, p?<?0.01) and postpartum weight retention (0.8?±?1.7 vs. 3.3?±?4.1?kg, p?<?0.01).

Conclusions?Regular participation in aerobic dance exercise can contribute to significantly reduce weight gain during pregnancy.     

Maternal/fetal eNOS-Glu298Asp genotypes and their influence on the severity,prognosis, and lipid profile of preeclampsia

Objectives: To analyze the contribution of maternal eNOS-Glu298Asp genotypes and also the association with fetal genotypes to the development of preeclampsia, prognosis, and maternal dyslipidemia.

Methods: Sixty-nine pairs of preeclamptic mothers/newborns and 94 pairs of normotensive mothers/newborns were genotyped for eNOS-Glu298Asp using PCR-RFLP methods.

Results: Women carriers of at least one Asp298 allele had a 1.53-fold (p?=?NS), 1.88-fold (p?=?NS), and 2.08-fold (p?=?.05), respectively, increased risk to develop PIH, mild, or severe preeclampsia. If both the mother and the newborn were carriers of the Asp298 allele, the risk for preeclampsia was 5.09-fold higher (p?p?=?.02) and LDL (mg/dl, 194.9?±?42.8 versus 144.98?±?54.84, p?=?.04) levels and lower HDL levels (mg/dl, 32.12?±?5.48 versus 57.84?±?20.59, p?=?.02) compared to noncarriers. Also, higher LDL levels (mg/dl, 188.76?±?46.61 versus 136.75?±?41.85, p?=?.03) and lower HDL levels (mg/dl, 32.8?±?5.64 versus 61.06?±?22.45, p?=?.02) were found in preeclamptic women with severe preeclampsia whose newborns were carriers of the Asp298 allele.

Conclusions: The eNOS-Glu298Asp variant (in mothers and newborns) in association with dyslipidemia could affect bioavailability of NO and could represent an increased risk for preeclampsia.     

The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography

Objectives: We aimed to evaluate the placental volume and placental mean gray value in preeclampsia and healthy placentas by using three-dimensional (3D) ultrasonography and Virtual Organ Computer-aided AnaLysis (VOCAL).

Methods: This case–control prospective study consisted of 27 singleton pregnancies complicated by preeclampsia and 54 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm³) was analyzed using the VOCAL imaging program, and 3D histogram was used to calculate the volumetric mean gray value (%).

Results: Preeclamptic and control group consisted of 27 (mean age: 28.90?±?5.95 years, mean gestation: 32.0?±?4.55 weeks) and 54 (mean age: 29.48?±?5.78 years, mean gestation: 32.61?±?4.23 weeks) singleton pregnancies, respectively. Placental volume was significantly smaller in preeclampsia (250.62?±?91.69 versus 370.98?±?167.82?cm³; p?=?0.001). Volumetric mean gray value of the placenta was significantly higher in preeclampsia (38.24?±?8.41 versus 33.50?±?8.90%; p?=?0.043). Placental volume was significantly correlated with the estimated fetal weight (r?=?0.319; p?=?0.003). There was negative significant relation between placental volume and umbilical artery pulsatility index, resistance index and systolic/diastolic ratio (r?=?–0.244, p?=?0.024; r?=?–0.283, p?=?0.005; r?=?–0.241, p?=?0.024, respectively).

Conclusions: Placental volume diminishes significantly in preeclampsia, whereas volumetric mean gray values increases. This may reflect the early alterations in preeclamptic placentas, which may help to understand the pathophysiology better.     

Relationship between nulliparity and preeclampsia may be explained by altered circulating soluble fms-like tyrosine kinase 1

Objective: To test the hypothesis that the risk of preeclampsia in nulliparous women may be due to an anti-angiogenic state. Methods: Maternal serum samples obtained in the third trimester from nulliparous (n?=?86) and multiparous (n?=?165) singleton uncomplicated pregnancies were analyzed for levels of angiogenic factors – soluble fms like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) by enzyme-linked immunosorbent assay (ELISA). Results: For nulliparous and multiparous pregnancies, serum sFlt1 levels were 12?732?±?832 and 10?162?±?666 (p?=?0.020), serum PlGF levels were 215?±?15 and 249?±?14 (p?=?0.093) (all reported as mean SD in pg/ml) and mean ratios of sFlt1/PlGF were 93?±?12 and 62?±?5 (p?=?0.023), respectively. Adjustment for maternal age and fetal birth weight did not alter the results. Conclusions: Nulliparous pregnancies had higher circulating sFlt1 levels and sFlt1/PlGF ratios than multiparous pregnancies, suggesting an association with an angiogenic imbalance. Taken together with the pathogenic role of anti-angiogenic factors in preeclampsia, our data may be one explanation for the epidemiological observation that nulliparity is a risk factor for the development of preeclampsia.