Andrea Luigi Tranquilli

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

There has never been a definite consensus on the classification and diagnostic criteria for the hypertensive disorders of pregnancy. This uncertainty is likely to have led to between-centre differences in rates of adverse maternal and foetal outcomes for the various hypertensive disorders in pregnancy, particularly pre-eclampsia. In 2000, the International Society for the Study of Hypertension in Pregnancy (ISSHP) recognised that this lack of consensus was one reason for controversies concerning counselling, management and documentation of immediate and remote pregnancy outcomes. Accordingly, the Society appointed a committee that reviewed available classifications and endorsed and published an international recommendation for how these disorders should be classified and diagnosed in pregnancy [1]. The major stumbling block remained whether or not proteinuria should be retained as a sine qua non for the diagnosis of pre-eclampsia; the Society recommended that a broad definition, at times not including proteinuria, could be applied for the clinical definition of pre-eclampsia whilst the inclusion of proteinuria would ensure more specificity around the diagnosis when reporting clinical criteria for patients enrolled in scientific research. The purpose of this document is to update ISSHP thinking on this subject.

The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP)

OBJECTIVE There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. METHODS We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. RESULTS There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. CONCLUSIONS A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature.

Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women

Qualitative and quantitative differences in the dietary habits of postmenopausal women were studied to assess their influence on bone health and osteoporosis. A total of 194 postmenopausal women were studied with forearm DEXA densitometry. 70 were osteoporotic and 124 served as controls. Women had been menopausal for 5-7 years, and had never been treated with hormone replacement or drug therapy. A 3-day dietary recall was completed on Sunday, Monday and Tuesday after the examination: the results were processed by computer and daily calcium, phosphorus and magnesium intakes were related to bone mineral content (BMC). Data were compared with Students t-test and significance was assessed at p < 0.05. Regression analysis was performed to correlate BMC and intake levels. The dietary intake of calcium, phosphorus and magnesium was significantly reduced in osteoporotic women and correlated with BMC. Calcium and magnesium intakes were lower than the recommended daily allowance even in normal women. The results suggest that nutritional factors are relevant to bone health in postmenopausal women, and dietary supplementation may be indicated for the prophylaxis of osteoporosis. Adequate nutritional recommendations and supplements should be given before the menopause, and dietary evaluation should be mandatory in treating postmenopausal osteoporosis.

Placental thrombomodulin expression in recurrent miscarriage

BackgroundEarly pregnancy loss can be associated with trophoblast insufficiency and coagulation defects. Thrombomodulin is an endothelial-associated anticoagulant protein involved in the control of hemostasis and inflammation at the vascular beds and its also a cofactor of the protein C anticoagulant pathway.DiscussionWe evaluate the Thrombomodulin expression in placental tissue from spontaneous recurrent miscarriage and voluntary abortion as controls. Thrombomodulin mRNA was determined using real-time quantitative polymerase chain reaction. Reduced expression levels of thrombomodulin were found in recurrent miscarriage group compared to controls (1.82-fold of reduction), that corresponds to a reduction of 45% (from control group Delta CT) of thrombomodulin expression in spontaneous miscarriage group respect the control groups.SummaryWe cannot state at present the exact meaning of a reduced expression of Thrombomodulin in placental tissue. Further studies are needed to elucidate the biological pathway of this important factor in the physiopathology of the trophoblast and in reproductive biology.

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. Clinically, they present with a variety of symptoms: excessive menstrual bleeding, dysmenorrhoea and intermenstrual bleeding, chronic pelvic pain, and pressure symptoms such as a sensation of bloatedness, increased urinary frequency, and bowel disturbance. In addition, they may compromise reproductive functions, possibly contributing to subfertility, early pregnancy loss, and later pregnancy complications. Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. This paper summarizes the available literature regarding the ultimate relative knowledge on pathogenesis of uterine fibroids and their interactions with endometrium and subendometrial myometrium.

Transdermal estradiol and medroxyprogesterone acetate in hormone replacement therapy are both antioxidants

We have evaluated the effects of the different components of hormone replacement therapy (HRT) on the production of free radicals in platelet membranes from menopausal women. The study included 12 women in menopause for at least 6 months to a maximum of 4 years. First, the effect was determined of progestin only during the administration of 20 mg/day medroxyprogesterone acetate for 5 days. The peroxide production level was measured on day 0 and day 5. The second set of experiments was carried out in the first month of cyclic HRT with transdermal estradiol 50 micrograms/day from day 1 to day 25 and medroxy-progesterone acetate from day 13 to day 25. In this experiment, the peroxide level was evaluated on days 0, 12 and 25. A significant reduction of peroxide level was observed after oral medroxyprogesterone acetate administration. During HRT, we observed a similar reduction in lipid oxidation at the peak of the estrogen effect, and a further decrease with the administration of medroxyprogesterone acetate. It is concluded that reduction of lipid peroxidation during HRT is not only due to estrogens, but also depends upon the combined action of sex steroids. This observation justifies not only the combined regimen (estrogens plus progestin) in HRT, but also the positive effects of progestins alone on patients who cannot use estrogens.

Transabdominal amnioinfusion in preterm premature rupture of membranes: a randomised controlled trial

Objective  To evaluate the role of transabdominal amnioinfusion in improving the perinatal outcomes of pregnancies complicated by preterm premature rupture of membranes (pPROM).

Potential Role of Culture Mediums for Successful Isolation and Neuronal Differentiation of Amniotic Fluid Stem Cells

In recent years, the use of stem cells has generated increasing interest in regenerative medicine and cancer therapies. The most potent stem cells derive from the inner cell mass during embryonic development and their use yields serious ethical and methodological problems. Recently, a number of reports suggests that another suitable source of multipotent stem cells may be the amniotic fluid. Amniotic fluid mesenchymal stem cells (AFMSCs) are capable of extensive self-renewal, able to differentiate in specialized cells representative of all three germ layers, do not show ethical restriction, and display minimal risks of teratomas and a very low immunogenity. For all these reasons, amniotic fluid appears as a promising alternative source for stem cell therapy. Their recent discovery implies a lack of knowledge of their specific features as well as the existence of a protocol universally recognized as the most suitable for their isolation, growth and long-term conservation. In this study, we isolated stem cells from six amniotic fluids; these cells were cultured with three different culture mediums [Mesenchymal Stem Cell Medium (MSCGM), PC-1 and RPMI-1640], characterized by cytofluorimetric analysis, and then either frozen or induced to neuronal differentiation. Even if the immunophenotype seemed not to be influenced by culture medium (all six samples cultured in the above-mentioned mediums expressed surface antigens commonly found on stem cells), cells showed different abilities to differentiate into neuron-like cells and to re-start the culture after short-long-term storage. Cells isolated and cultured in MSCGM showed the highest proliferation rate, and formed neuron-like cells when sub-plated with neuronal differentiation medium. Cells from PC-1, on the contrary, displayed an increased ability to re-start culture after short-long term storage. Finally, cells from RPMI-1640, even if expressing stem cells markers, were not able to differentiate in neuron-like cells. Further studies are still needed in order to assess the effective role of culture medium for a successful isolation, growth, differentiation and storage of AFMSCs, but our data underline the importance of finding a universally accepted protocol for the use of these cells.

Amniotic vascular endothelial growth factor (VEGF) and nitric oxide (NO) in women with subsequent preeclampsia.

OBJECTIVE To assess whether amniotic fluid concentrations of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in early pregnancy correlate to subsequent preeclampsia. STUDY DESIGN We performed a retrospective study to assess VEGF and NO on the second trimester amniotic fluid of 15 healthy women, and 15 women who subsequently developed preeclampsia. RESULTS In women with subsequent preeclampsia, both VEGF (213.19+/-78.42 pg/ml) and NO concentrations (4.31+/-1.02 micromol/mg creatinine) were significantly lower than healthy controls (VEGF 255.05+/-88.66 pg/ml; NO 5.02+/-1.57 microg/mg creatinine; P<0.05). CONCLUSIONS Our findings suggest that reduced VEGF may be responsible, at least in part, for the impaired vascular development which occurs in preeclampsia. Low concentrations of VEGF and NO in the second trimester may represent an impaired stimulus to vascular formation and endothelial regulation that induce placental disease and preeclampsia.

Number and size of uterine fibroids and obstetric outcomes

Abstract Objective: Estimating the impact of sonographically identified multiple or large (≥5 cm in diameter) fibroids on obstetric outcomes. Methods: Retrospective cohort study of 219 women with uterine fibroids (identified on a routine second-trimester ultrasound survey over a 3-year period, 2010–2012) and their age-matched controls. Inclusion criteria were singleton pregnancy, delivery at >24 weeks of gestation and no pathological conditions (chronic hypertension, gestational diabetes or pre-existing diabetes mellitus, uterine anomalies or fetal malformations). Results: Compared to women with no fibroids, women with multiple fibroids (n = 34) had a significantly higher rate of preterm birth (29.4% versus 5%, p < 0.001), cesarean section (73.5% versus 37%, p < 0.001) and breech presentation (11.8% versus 2.7%, p = 0.04). Women with large fibroids (n = 48) had a higher rate of preterm birth (16.7% versus 5%, p = 0.01) and pPROM (10.4% versus 0.5%, p < 0.001). By multivariate analysis, only multiple fibroids and previous preterm birth showed an independent significant association with preterm birth (OR = 7.37, 95% CI 2.50–21.68 and OR = 13.01, 95% CI 3.56–47.52, respectively). Conclusions: Women with uterine fibroids are at an increased risk of obstetric complications. In particular, multiple rather than large fibroids are associated with a significantly increased risk of preterm birth and cesarean delivery while large fibroids are associated with a higher risk of pPROM. No correlation with IUGR, placenta previa or placental abruption was found.