G. Mello

Thrombophilia Is Significantly Associated With Severe Preeclampsia Results of a Large-Scale, Case-Controlled Study

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.

D-DIMER CONCENTRATIONS DURING NORMAL PREGNANCY, AS MEASURED BY ELISA

In pregnant women a number of changes in blood clotting and fibrinolysis proteins have been reported so indicating the existence of a state of hypercoagulability. In addition to fibrinogen and antithrombin III (AT), D-dimer is frequently checked during pregnancy, in particular during at risk pregnancy, but the exact pattern of D-dimer modifications during uncomplicated pregnancy is not definitively described. The aim of this study was to establish the range values in three different periods of uncomplicated pregnancy (A: 1-20 wks; B: 21-30 wks; C: 31-40 wks). We measured plasma levels of D-dimer, clottable fibrinogen and AT in 108 consecutive normal pregnant women aged 16 to 42 years. In period A, the range of D-dimer values was 43-211 ng/mL, not different from controls, while fibrinogen levels were significantly higher (p < 0.05) than in matched non pregnant women. Mean D-dimer levels were higher in periods B (p < 0.05) and C (p < 0.05) vs period A. Similarly, mean fibrinogen levels were found more elevated in periods B and C vs period A (p < 0.05). A significant correlation was found between fibrinogen and D-dimer levels (p < 0.001). No differences in AT levels were found among the three periods of pregnancy. The results of this study indicate that levels of D-dimer up to 685 micrograms/L may be reached at the end of physiological pregnancy. This fact should be taken into account in the evaluation of hemostatic studies performed in uncomplicated and complicated pregnant women.

Maternal-Fetal Flow, Negative Events, and Preeclampsia: Role of ACE I/D Polymorphism

Abstract—The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (P =0.0002) and allele frequency (P <0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (P =0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. The current study shows that the ACE I/D polymorphism affects uteroplacental and umbilical flows and the recurrence of an adverse pregnancy outcome in women with history of preeclampsia.

VEGF expression in the placenta from pregnancies complicated by hypertensive disorders

Objective  To determine the expression of VEGF in the placental tissue from pregnancies complicated by hypertension disorders of different clinical severity.

Thyroid autoimmunity and its association with non-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia

Following the observation that non-organ-specific antibodies are related with pregnancy loss and preeclampsia, the role of organ-specific antibodies is currently being extensively investigated. The aim of this study was on the one hand to evaluate the incidence of antithyroid antibodies in a study group of 69 women with a history of early pregnancy loss (subgroup 1), foetal death (subgroup 2) or preeclampsia (subgroup 3) and in a control group, on the other hand to assess the possible association of these autoantibodies with non-organ-specific antibodies and subclinical alterations of thyroid function in the study group. Antithyroid antibodies were present in 26/69 (37.7%) women of the study group (37.9% in subgroup 1; 40.9% in subgroup 2; 33.3% in subgroup 3) and in 10/69 (14.5%) of controls, the difference being statistically significant. A significant difference in the distribution of antibodies to thyroglobulin and thyroid peroxidase was found in subgroup 2. In the study group, the incidence of antiphospholipid antibodies was not significantly different in women positive (26.9%) and negative (34.9%) for antithyroid antibodies. Also, the overall incidence of subclinical alterations of thyroid function in the study group was significantly different in women positive (53.8%) and negative (16.2%) for thyroid autoimmunity (P<0.02). The results of this study seem to confirm the association between thyroid autoimmunity and obstetric complications and suggest the usefulness of undertaking prospective studies in order to evaluate the reproductive outcome of women with a history of recurrent abortion, foetal death or preeclampsia and positivity for antithyroid antibodies.

BLOOD CLOTTING ACTIVATION DURING NORMAL PREGNANCY

Pregnancy is considered as a hypercoagulable state and an increased incidence of thromboembolic phenomena has been reported in pregnant women. Relevant changes in the hemostatic mechanism have been reported during physiological pregnancy: briefly, increased levels of coagulation factors, enhanced thrombin generation and suppression of fibrinolysis are commonly found in women with uncomplicated pregnancy. We recently described progressive increases in fibrinogen and D-dimer plasma levels during normal pregnancy. The increase in D-dimer levels makes difficult their interpretation for the exclusion of thromboembolic phenomena in pregnancy. The behavior of prothrombin fragment 1+2 (F1+2) levels during physiological pregnancy is scarcely known. The aim of this preliminary study was to establish range values of F1+2 plasma levels for different periods of normal pregnancy.

Usefulness of screening for congenital or acquired hemostatic abnormalities in women with previous complicated pregnancies.

Activated protein C resistance (APCR) is a common cause of familial thrombophilia and venous thrombosis. The aim of the study was to investigate the prevalence of APCR associated with factor V Leiden mutation and its relevance in comparison to other risk factors for thromboembolic disorders in women with a history of previous complicated pregnancies (history of fetal loss in the second and third trimester n = 34, preeclampsia n = 46). The frequency of APCR was significantly higher in women with a history of fetal loss and preeclampsia (23.5 and 26.1%, respectively) compared with a control group (3.8%). The prevalence of antithrombin, protein C and protein S deficiencies and the presence of antiphospholipid antibodies were also investigated: the prevalence of at least one disorder was 41.2% in the group with previous fetal loss, 37.0% in the group with previous preeclampsia and 7.5% in the control group.

Use of insulin detemir in pregnancy: a report on 10 Type 1 diabetic women

bromatosis 1 ⁄ Noonan syndrome associated with Hashimoto’s thyroiditis and vitiligo. Acta Derm Venereol 2006; 86: 80–81. 6 Zaka-ur-Rab Z, Chopra K. Diabetes mellitus in neurofibromatosis I: an unusual presentation. Indian Pediatr 2005; 42: 185–186. 7 Tekin F, Ozutemiz O, Carcurgan S, Ilter T. Autoimmune haemolysis as an unusual cause of anaemia in von Recklinghausen’s disease. Neth J Med 2004; 62: 337–339. 8 Corominas H, Guardiola JM, Matas L, Vázquez G. Neurofibromatosis and systemic lupus erythematosus. A matter of coincidence? Clin Rheumatol 2003; 22: 496–497. 9 Migita K, Kawabe Y, Mori M, Hirose R, Kimura H, Hamada H et al. Mixed connective tissue disease associated with Von Recklinghausen’s neurofibromatosis. Intern Med 2001; 40: 363– 364. 10 Tarrass F. Focal and segmental glomerulosclerosis and Von Recklinghausen’s neurofibromatosis: coincidental or associated? Saudi J Kidney Dis Transpl 2008; 19: 453–454. 11 Yesudian PD, Wilson NJ, Parslew R. Bullous pemphigoid and neurofibromatosis—a chance association requiring special vigilance. Clin Exp Dermatol 2000; 25: 658–659. 12 Feuillet L, Boudinet H, Casseron W, Uzenot D, Pelletier J, Cherif A. Multiple sclerosis associated with neurofibromatosis type I. Rev Neurol 2004; 160: 447–451.

D-Dimer plasma levels during normal pregnancy measured by specific ELISA

A progressive increase in D-dimer plasma levels together with an increase in fibrinogen has been previously reported during normal pregnancy. However, significantly different D-dimer levels have been observed in different assays, due to different specificity of the antibodies employed. The aim of this study was to verify the increase in fibrin degradation product levels during normal pregnancy, using a recently introduced specific D-dimer ELISA. We determined D-dimer (ELISA) and fibrinogen (clotting method) plasma levels in 63 normal pregnant women, during three different periods of pregnancy (A, 7–20 weeks; B, 21–30 weeks; C, > 30 weeks). During period A, D-dimer plasma levels (range 2–103 ng/ml) showed an insignificant increase compared with a control group of non-pregnant women (range 2–73 ng/ml). During periods B and C, we observed an increase in D-dimer level (P<0.0001) compared with period A, with a significant correlation between D-dimer levels and gestational age (P<0.0001). Period A fibrinogen levels (range 3.24–6.43 g/l) were significantly higher (P<0.0001) than in controls (range 2.31–4.71 g/l), with a further increase in periods B and C. In conclusion, we confirmed a progressive increase in plasma concentrations of fibrin degradation product during normal pregnancy, but D-dimer levels were significantly lower than those reported in the literature for other ELISAs.

Volatile Signals During Pregnancy: A Possible Chemical Basis for Mother–Infant Recognition

Human pheromones play a role in regulating relationships and apparently influence partner choice and mother–infant recognition. We analyzed the chemical content of volatiles from sweat patch samples from the para-axillary and nipple–areola regions of women during pregnancy and after childbirth. Solid phase microextraction was used to extract the volatile compounds, which were then characterized and quantified by gas chromatography–mass spectrometry. During pregnancy, women developed a distinctive pattern of five volatile compounds common to the para-axillary and nipple–areola regions (1-dodecanol, 1-1′-oxybis octane, isocurcumenol, α-hexyl-cinnamic aldehyde, and isopropyl myristate). These compounds were absent outside pregnancy and had slightly different patterns in samples from the two body areas. Differentiation of the volatile patterns among pregnant women may help newborns to distinguish their own mothers.