What is the role of glycemic control in the development of preeclampsia among women with type 1 diabetes?

OBJECTIVE: To investigate the role of glycemic control in development of preeclampsia (PE) in women with type 1 diabetes mellitus (T1DM). METHODS: An observational case-control study comparing 244 women with type 1 diabetes and 488 controls was conducted. Among women with T1DM HbA1c, average daily glucose values, fasting, preprandial, 1-hour and 2-hour postprandial glucose levels, and daily 3 meals postprandial glucose areas were evaluated. Uterine artery pulsatility indices (PI) at 16, 20, 24 weeks' gestation were obtained. Data analysis included rates of PE in both groups, and association between glycemic control, uterine artery PI and development of PE among women with T1DM. RESULTS: PE developed in 13.1% of diabetic women and in 3.5% of women in the control group (odds ratio 4.2; 95% CI 2.2-8.1). In multivariate logistic regression analysis, HbA1c in the 1st trimester, mean daily glucose level in the 1st and 2nd trimester, daily 3 meal postprandial glucose area in the 1st and 2nd trimester, and the uterine arteries PI at 24 weeks' gestation were found to be associated with development of PE. The uterine arteries PI showed a significant positive correlation with the 3 meal postprandial glucose area at 16, 20, 24 weeks. CONCLUSION: In women with T1DM, poor glycemic control early in pregnancy is associated with an increased risk of subsequent PE. An association between poor placentation, as indicated by the increased PI of uterine arteries, and a maternal metabolic factor, that is the 3 meal post-prandial glucose area, has been shown, supporting the increased rate of PE among women with T1DM.

Fetal Growth Restriction: Does an Integrated Maternal Hemodynamic-Placental Model Fit Better?

In recent years, a growing interest has arisen regarding the possible relationship between adverse pregnancy outcomes (APOs) and inadequate maternal hemodynamic adaptations to the pregnancy. A possible association between "placental syndromes," such as preeclampsia (PE) and fetal growth restriction (FGR), and subsequent maternal cardiovascular diseases (CVD) later in life has been reported. The two subtypes of FGR show different pathogenetic and clinical features. Defective placentation, due to a poor trophoblastic invasion of the maternal spiral arteries, is believed to play a central role in the pathogenesis of early-onset PE and FGR. Since placental functioning is dependent on the maternal cardiovascular system, a pre-existent or subsequent cardiovascular impairment may play a key role in the pathogenesis of early-onset FGR. Late FGR does not seem to be determined by a primary abnormal placentation in the first trimester. The pathological pathway of late-onset FGR may be due to a primary maternal cardiovascular maladaptation: CV system shows a flat profile and remains similar to those of non-pregnant women. Since the second trimester, when the placenta is already developed and increases its functional request, a hypovolemic state could lead to placental hypoperfusion and to an altered maturation of the placental villous tree and therefore to an altered fetal growth. Thus, this review focalizes on the possible relationship between maternal cardiac function and placentation in the development of both early and late-onset FGR. A better understanding of maternal hemodynamics in pregnancies complicated by FGR could bring various benefits in clinical practice, improving screening and therapeutic tools.

Immunological changes associated with adenomyosis: a systematic review.

BACKGROUND: Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health and quality of life of women. Histologically, it is defined as the presence of ectopic endometrial islets within the myometrium. Its pathogenesis has not yet been elucidated and several pieces of the puzzle are still missing. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. Here, we review current knowledge on the immunological changes in adenomyosis, with the aim of further elucidation of the pathogenesis of this disease. OBJECTIVE AND RATIONALE: The objective was to systematically review the literature regarding the role of the immune system in development of adenomyosis in the inner and the outer myometrium, in humans. SEARCH METHODS: A systematic review of published human studies was performed in MEDLINE, EMBASE and Cochrane Library databases from 1970 to February 2019 using the combination of Medical Subject Headings (MeSH): Adenomyosis AND ('Immune System' OR 'Gonadal Steroid Hormones'), and free-text terms for the following search terms (and their variants): Adenomyosis AND (immunity OR immune OR macrophage OR 'natural killer cell' OR lymphocyte* OR leucocyte* OR HLA OR inflammation OR 'sex steroid' OR 'epithelial to mesenchymal transition' OR 'EMT'). Studies in which no comparison was made with control patients, without adenomyosis (systemic sample and/or eutopic endometrium), were excluded. OUTCOMES: A total of 42 articles were included in our systematic review. Changes in innate and adaptive immune cell numbers were described in the eutopic and/or ectopic endometrium of women with adenomyosis compared to disease-free counterparts. They mostly described an increase in lymphocyte and macrophage cell populations in adenomyosis eutopic endometrium compared to controls. These observations underscore the immune contributions to the disease pathogenesis. Thirty-one cytokines and other markers involved in immune pathways were studied in the included articles. Pro-inflammatory cytokines (interleukin (IL) 6, IL1ß, interferon (IFN) α, tumor necrosis factor α, IFNγ) as well as anti-inflammatory or regulatory mediators (IL10, transforming growth factor ߅) were found to be elevated in the eutopic endometrium and/or in the ectopic endometrium of the myometrium in women with adenomyosis compared to controls. Moreover, in women affected by adenomyosis, immunity was reported to be directly or indirectly linked to sex steroid hormone aberrations (notably changes in progesterone receptor in eutopic and ectopic endometrium) in three studies and to EMT in four studies. WIDER IMPLICATIONS: The available literature clearly depicts immunological changes that are associated with adenomyosis. Both systemic and local immune changes have been described in women affected by adenomyosis, with the coexistence of changes in inflammatory as well as anti-inflammatory signals. It is likely that these immune changes, through an EMT mechanism, stimulate the migration of endometrial cells into the myometrium that, together with an endocrine imbalance, promote this inflammatory process. In light of the considerable impact of adenomyosis on women's health, a better understanding of the role played by the immune system in adenomyosis is likely to yield new research opportunities to better understand its pathogenesis.

An objective scoring method to evaluate image quality of middle cerebral artery Doppler.

Objective: To validate an objective scoring system for middle cerebral artery (MCA) pulsed wave Doppler images.Method: From an image database of routine 36-week scans, a random sample of MCA Doppler images was selected. Two reviewers rated the images subjectively as acceptable or unacceptable. Subsequently they used an objective 6-point image scoring system and awarded one point for each of the following: (1) anatomical site, (2) magnification, (3) angle of insonation, (4) image clarity, (5) sweep speed adjustment, and (6) velocity scale and baseline adjustment. Image scores 4-6 were defined as good quality whereas 0-3 as poor. The subjective and objective agreement between the two reviewers was compared using the adjusted Kappa statistic.Results: A total of 124 images were assessed. Using objective scoring the agreement rate between reviewers increased to 91.9% (κ = 0.839) compared to subjective agreement 75.8% (κ = 0.516). The agreement for each criterion was: anatomical site 91.1% (κ = 0.823), magnification 95.2% (κ = 0.903), clarity 83.9% (κ = 0.677), angle 96.0% (κ = 0.919), sweep speed 98.4% (κ = 0.968), and velocity scale and baseline 94.4% (κ = 0.887).Conclusion: Objective assessment of MCA Doppler images using a 6-point scoring system has greater interobserver agreement than subjective assessment and could be used for MCA Doppler quality assurance.

Using fetal abdominal circumference growth velocity in the prediction of adverse outcome in near-term small-for-gestational-age fetuses.

OBJECTIVE: To investigate whether abdominal circumference growth velocity (ACGV) improves the prediction of perinatal outcome in small-for-gestational-age (SGA) fetuses beyond that afforded by estimated fetal weight (EFW) and cerebroplacental ratio (CPR). METHODS: A cohort of 235 singleton SGA fetuses at 36-38 weeks' gestation was examined. ACGV, EFW and CPR centiles were calculated. ACGV centile was determined using data from a large database of 19-21- and 36-38-week scans in an unselected population. Binary variables of ACGV < 10th , EFW < 3rd and CPR < 5th centiles were defined as abnormal. Two composite adverse outcomes (CAO) were explored: CAO-1 defined as at least one of umbilical artery pH < 7.10, 5-min Apgar score < 7 or neonatal unit admission, and CAO-2 that included in addition hypoglycemia, intrapartum fetal distress and perinatal death. Univariate and multivariate logistic regression analyses were performed to analyze the relationship between the three risk factors and their predictive value for CAO. The change in screening performance afforded by adding ACGV to EFW and CPR was assessed and receiver-operating characteristics (ROC) curves were calculated. RESULTS: ACGV < 10th centile was an independent risk factor for CAO. The sensitivity, specificity, positive and negative likelihood ratios of a predictive model based on EFW < 3rd centile and CPR < 5th centile were, respectively, 51%, 70%, 1.71 and 0.69 for CAO-1 and 41%, 70%, 1.39 and 0.83 for CAO-2. After addition of ACGV < 10th centile to the model, the respective values were 82%, 46%, 1.54 and 0.38 for CAO-1 and 71%, 47%, 1.34 and 0.62 for CAO-2. Using continuous variables, the areas under the ROC curves improved marginally from 0.669 (95% CI, 0.604-0.729) to 0.741 (95% CI, 0.677-0.798) for CAO-1 and from 0.646 (95% CI, 0.580-0.707) to 0.700 (95% CI, 0.633-0.759) for CAO-2 after addition of ACGV to the model. CONCLUSIONS: ACGV is a risk factor for adverse neonatal outcome that is independent of EFW and of CPR, although any improvement in the prediction of adverse outcome is not statistically significant. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Placental and maternal serum activin A in spontaneous and induced labor in late-term pregnancy.

PURPOSE: Feto-placental unit represents an important source of activin A, a member of transforming growth factors-ß involved in the mechanisms of labor. No evidences are available on activin A in pregnancies beyond 41 weeks of gestation, where induction of labor is often required. The present study aimed to evaluate activin A maternal serum levels and placental mRNA expression in term and late-term pregnancy, with spontaneous or induced labor, and its possible role to predict the response to labor induction. METHODS: Maternal serum samples and placental specimens were collected from women with singleton pregnancy admitted for either term spontaneous labor (n = 23) or induction of labor for late-term pregnancy (n = 41), to evaluate activin A serum levels and placental mRNA expression. Univariate and multivariate analyses on activin A serum levels, maternal clinical parameters, and cervical length were conducted in women undergoing induction of labor. RESULTS: Maternal serum activin A levels and placental activin A mRNA expression in late-term pregnancies were significantly higher than at term. Late-term pregnancies who did not respond to induction of labor showed significantly lower levels of activin A compared to responders. The combination of serum activin A and cervical length achieved a sensitivity of 100% and a specificity of 93.55% for the prediction of successful induction. CONCLUSION: Late-term pregnancy is characterized by hyperexpression of placental activin A and increased maternal activin A secretion. By combining maternal serum activin A levels with cervical length, a good predictive model for the response to induction of labor was elaborated.

Placenta expresses anti-Müllerian hormone and its receptor: Sex-related difference in fetal membranes.

INTRODUCTION: Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-ß superfamily, playing a role in sexual differentiation and recruitment. Since a correlation exists between AMH serum levels in cord blood and fetal sex, the present study aimed to identify mRNA and protein expression of AMH and AMHRII in placenta and fetal membranes according to fetal sex. METHODS: Placenta and fetal membranes samples (n = 40) were collected from women with singleton uncomplicated pregnancies at term. Identification of AMH protein in placenta and fetal membranes was carried out by immunohistochemistry and AMH and AMHRII protein localization by immunofluorescence, while mRNA expression was assessed by quantitative real-time PCR. RESULT: AMH and AMHRII mRNAs were expressed by placenta and fetal membranes at term, without any significant difference between males and females. Placental immunostaining showed a syncytial localization of AMH without sex-related differences; while fetal membranes immunostaining was significantly more intense in male than in female fetuses (p < 0,01). Immunofluorescence showed an intense co-localization of AMH and AMHRII in placenta and fetal membranes. DISCUSSION: The present study for the first time demonstrated that human placenta and fetal membranes expresses and co-localizes AMH and AMHRII. Although no sex-related difference was found for the mRNA expression both in placenta and fetal membranes, a most intense staining for AMH in male fetal membranes supports AMH as a gender specific hormone.

Anterior placental location influences onset and progress of labor and postpartum outcome.

INTRODUCTION: The aim of the study is to evaluate whether placental location at term is associated with delivery outcome. METHODS: A prospective study including 2354 patients with singleton pregnancy at term admitted for vaginal delivery was conducted. Placental position was determined before delivery by ultrasonographic examination performed transabdominally with women in the supine position. Maternal characteristics and delivery outcome such as premature rupture of membranes, induction of labor, mode and gestational age at delivery, indication for cesarean section, duration of the third stage, postpartum hemorrhage (PPH) and manual removal of placenta were correlated with anterior, posterior or fundal placental locations. RESULTS: Among women enrolled: i) 1164 had an anterior placenta, ii) 1087 a posterior placenta, iii) 103 a fundal placenta. Women with anterior placenta showed: i) a higher incidence of induction of labor (p = 0.0001), especially for postdate pregnancies and prolonged prelabor rupture of membranes (p < 0.0001), ii) a higher rate of cesarean section rate for failure to progress in labor (p = 0.02), iii) a prolonged third stage (p = 0.01), iv) a higher incidence of manual removal of placenta (p = 0.003) and a higher rate of PPH in vaginal deliveries (p = 0.02). DISCUSSION: The present study showed the influence of anterior placental location on the course of labor, with a later onset of labor, a higher rate of induction and cesarean section and postpartum complications. The reason for this influence on labor and delivery complications remains to be elucidated.