Effectiveness of emergency cerclage in cervical insufficiency.

OBJECTIVE: To assess the effectiveness of emergency cerclage versus conservative management in improving obstetric and neonatal outcomes in women with clinically evident cervical insufficiency. METHODS: Retrospective cohort study conducted on all women with a single viable pregnancy diagnosed with cervical insufficiency between the 14th and 24th gestational week without pPROM, clinical chorioamnionitis, vaginal bleeding, treatment-resistant uterine contractions or life-incompatible fetal anomalies, from January 2009 to December 2014. Obstetric and neonatal outcomes were compared between women who underwent cerclage and those who refused, preferring a conservative therapy. RESULTS: Eighteen women underwent emergency cerclage and 19 were managed with a conservative therapy. Mean gestational age at delivery, time from diagnosis to delivery and rate of term birth were significantly higher in the first cohort. Those variables show a linear inverse correlation with the degree of cervical dilatation, with better outcomes in patients who underwent cerclage with a dilatation lower than 5.0 cm. No difference in mode of delivery were found. CONCLUSION: Emergency cerclage is a valid therapeutic option between the 14th and 24th gestational week in presence of cervical insufficiency when signs of premature labour or infection are not present, with lower expectations with a dilatation greater than 5 cm.

Preeclampsia: what could happen in a subsequent pregnancy?

IMPORTANCE: Preeclampsia is the most common type of the hypertensive disorders of pregnancy, affecting nearly 5% of pregnant women. The risk of recurrence influences the choices of parents regarding subsequent pregnancies and necessitates the counseling of obstetricians. OBJECTIVE: To review the risk of recurrence of hypertensive disorders in a subsequent pregnancy. EVIDENCE ACQUISITION: Women with a history of preeclampsia are at an increased risk of preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies. The magnitude of this risk is dependent on gestational age at the time of disease onset, severity of disease, and presence or absence of preexisting medical disorders. RESULTS: For preeclamptic women with severe features in an initial pregnancy, recurrence rates for any type of preeclampsia are very high, approaching 50% in some studies. Significant maternal and fetal complications are more common in recurrent preeclampsia compared with an initial episode. Because women with previous preeclampsia are at an increased risk for adverse pregnancy outcomes (preterm delivery, fetal growth restriction, abruptio placentae, and fetal death) in subsequent pregnancies, we recommend more frequent monitoring for signs and symptoms of severe hypertension or preeclampsia than that recommended for normal pregnancy. CONCLUSIONS: The best option is to review the existing literature with patients, allow them to make informed decisions, and provide them the best available prenatal care.

Amniotic coenzyme Q10: is it related to pregnancy outcomes?

Coenzyme Q10 (CoQ10 or ubiquinone) is an essential component of the mitochondrial electron transport chain and is also present in various cellular membranes and in plasma lipoproteins. Diabetes, cardiovascular, neurodegenerative, and preeclampsia diseases are all associated with an alteration of CoQ10 level or its redox status. During pregnancy, we note that the plasma content of CoQ10 is significantly higher than amniotic. In the fetal growth restriction group, amniotic total CoQ10 levels were significantly higher versus healthy, while the amniotic oxygen radical absorbing capacity level was significantly lower. A significant negative correlation was observed between amniotic total CoQ10 and birthweight. Our observation leads to the hypothesis that the amniotic midtrimester CoQ10 content may be a marker of subsequent obstetric complications.

Nifedipine versus labetalol in the treatment of hypertensive disorders of pregnancy.

PURPOSE: To assess the maternal and fetal outcomes of pregnancies affected by hypertensive disorders treated with nifedipine versus labetalol. METHODS: A retrospective study in hypertensive patients treated during pregnancy with nifedipine or labetalol was conducted. After the charts review the patients were divided in the four groups: gestational hypertension (113 patients); mild preeclampsia (77 patients); severe preeclampsia (31 patients); HELLP syndrome (21 patients). The pregnancy and neonatal records were analyzed by paired and unpaired t test. RESULTS: We found that there was an higher rate of intrauterine growth restriction infants among women treated with labetalol compared with those treated with nifedipine (38.8 vs. 15.5 %; p < 0.05), but only in the subgroup of women affected by Gestational Hypertension and Mild Preeclampsia. In this group was also higher the rate of fetal worsening assessed by fetal heart rate tracing (33.3 vs. 14.2 %; p < 0.05). No neonatal malformations and no differences in the rate of adverse side effects were observed. CONCLUSIONS: Antihypertensive therapy in pregnancy with Labetalol may have the potential to impair fetal behavior in low degrees hypertensive diseases of pregnancy. Optimal care must balance the potentially conflicting risks and benefits to mother and fetus.

The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage.

OBJECTIVE: To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM). STUDY DESIGN: Trophoblasts were obtained during uterine evacuation from 11 women with RM and from 20 healthy pregnant women undergoing elective termination of pregnancy, who served as controls. The array was performed using GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015 membranes. Data were confirmed by quantitative real-time PCR. The Mann-Whitney U test was performed for statistical analysis. RESULTS: Microarray analysis identified three genes that were differentially expressed between RM patients and controls. We observed significant downregulation of Transforming Growth Factor beta 3 (TGF-ß3) and Interleukin 25 (IL-25) (5-fold reduction and 2.5-fold reduction, respectively) and significant upregulation of CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold increase) in women with RM compared with controls. The median ΔC(t) of TGF-ß3 was 8.2 (interquartile range, 7.67-8.9) in RM patients vs. 5.85 (interquartile range, 5.3-6.09) in controls; the median ΔC(t) of IL-25 was 5.18 (interquartile range, 4.46-5.76) in RM patients vs. 3.85 (interquartile range, 3.6-4.51) in controls, and the median ΔC(t) of CD-25 was 9.62 (interquartile range, 7.81-12.42) in RM patients vs. 12.44 (interquartile range, 11.02-13.86) in controls. DISCUSSION: Our results suggest that the immunological and inflammatory regulation mechanisms of the placental environment play a key role in recurrent miscarriage. The observed trophoblast cytokine expression pattern at the maternal-fetal interface confirms the immunotrophic theory, as demonstrated by a switch from a T-helper-1 (Th1) profile to a T-helper-2 (Th2) profile in women who experience recurrent miscarriages.

Preeclampsia: No longer solely a pregnancy disease.

Preeclampsia, the leading cause of maternal and perinatal morbidity and mortality, has been recently considered not only a pregnancy disease but also a risk factor for developing diseases later in life. Preeclampsia is becoming a disease of interest to internists and not just obstetricians. Women who have had preeclampsia seem to be at higher risk of premature death, mortality from ischemic heart disease, cardiovascular diseases including ischemic heart disease and hypertension, fatal and non-fatal stroke, venous thromboembolism, renal failure, type 2 diabetes mellitus, hypothyroidism, and cognitive defects, although they appear surprisingly protected from cancer. Furthermore, having had preeclampsia is a problem not only for the mother's future health, but it also affects the offspring's adult health. Children born from preeclamptic pregnancies are more prone to hypertension, insulin resistance and diabetes mellitus, neurological problems, stroke, and mental disorders along their life. Whether preeclampsia is a risk factor for disease later in life or it creates long-term organ damage is an intriguing question. This review analyzes recent epidemiological evidence of the long-term outcomes of preeclampsia and the background mechanisms of this phenomenon. Understanding the etiological background may provide guidance for the prevention and follow-up of women who experience preeclampsia.

The origin of pre-eclampsia: from decidual "hyperoxia" to late hypoxia.

Normal gestation implants on a relatively hypoxic deciduas so that trophoblast deeply invades endometrium and angiogenesis seeks for oxygen supply. If implantation occurs before those hypoxic conditions occur, trophoblast invasion is defective, due to the relatively high oxygen tension in the decidual environment, laying the foundations for subsequent pre-eclampsia.

Alpha-hemoglobin-stabilizing protein (AHSP) in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome, intrauterine growth restriction (IUGR) and fetal death.

OBJECTIVE: Alpha hemoglobin-stabilizing protein (AHSP) inhibits the production of reactive oxygen species in various cells, including erythrocytes. Reduced AHSP can mean reduced protection from stressors. Our objective was to investigate whether AHSP is involved in the response to stress in pregnancy. STUDY DESIGN: Placentas were collected from normal term pregnancies (n = 10) and pregnancies complicated by HELLP (n = 10), intrauterine growth restriction (IUGR; n = 10) or fetal death (IUFD; n = 6). AHSP messenger RNA (mRNA) and protein were determined using real time quantitative polymerase chain reaction (PCR) and Western blot, respectively. All statistical analyses were performed by using the GraphPad Prism Software. Differences were considered significant at p < 0.05. RESULTS: Placental AHSP mRNA level in HELLP (4.16E10(-4) +/- 1.77) and IUFD (4.19E10(-4) +/- 3.37) were significantly decreased compared with controls (28.47E10(-4) +/- 14.86; p < 0.01), whereas levels in the IUGR group (7.55E10(-4) +/- 6.4) showed a trend toward being lower but the difference did not reach statistical significance. Western blot analysis results indicate a no significant increase of ASHP protein in the HELLP syndrome group and a significant decrease in the IUFD group compared with controls. There was no significant difference between the IUGR and control groups. CONCLUSION: ASHP mRNA expression in the placenta is decreased in complicated pregnancies, and it may be involved in the pathogenic mechanisms leading to the adverse pregnancy outcome.

Inflammatory cytokines patterns in the placenta of pregnancies complicated by HELLP (hemolysis, elevated liver enzyme, and low platelet) syndrome.

OBJECTIVE: We investigated the expression pattern and the role of inflammatory cytokines and their receptors in the placentas of pregnancy with HELLP syndrome. STUDY DESIGN: Placentas were collected after cesarean section, 10 from normal pregnancy and 10 from HELLP. The array was performed with GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015. The data were confirmed by quantitative real-time PCR. The Student's t test was used for statistical analysis. RESULTS: Macroarray analysis identified 14 cytokines differentially expressed. PCR confirmed that only IL-10, IL-6-receptor, and TGF-beta3 were increased, whilst CCL18, CXCL5, and IL-16 were significantly decreased, in HELLP. CONCLUSION: The regulation of cytokines involved in angiogenesis and adaptive immune responses may be critical for the placental vascular dysfunction. Our data support the hypothesis that HELLP syndrome could be a placental inflammatory response which leads to a systemic and endothelial dysfunction.