Continuous electronic fetal heart monitoring versus intermittent auscultation during labor: Would the literature outcomes have the same results if they were interpreted following the NICHHD guidelines?

BACKGROUND: All guidelines regarding electronic fetal heart monitoring (EFM) before 2008 were designed to avoid more hypoxia than acidosis. In addition, the results of the Cochrane meta-analysis of 2013 do not show a significant improvement in neonatal outcomes using EFM or intermittent auscultation (IA). OBJECTIVES: We retrospectively evaluated the results on delivery outcomes arising from a comparison between EFM and IA during labor of 2 specific and high-quality trials. We hypothesized that revisiting the delivery outcomes through the adoption of the recent National Institute of Child Health and Human Development (NICHHD) guidelines, the reported delivery outcomes would be different. MATERIAL AND METHODS: The study retrospectively evaluated the results on delivery outcomes arising from the comparison between EFM and IA during labor of the "Dublin trial" and "Vintzileos trial" published, respectively, in 1985 and 1993. A translational model was constructed to recalculate these results, applying a correction factor to estimate the number of pathological patterns using the NICHHD guidelines for EFM. RESULTS: After the reevaluation of the 2 trials using the proposed correction factor, the comparison of the recalculated cesarean section and operative delivery rates for fetal distress between EFM and IA group were no longer statistically significant, both in the Dublin trial and Vintzileos trial. Even the comparison of the recalculated incidence of the rate of non-reassuring fetal heart rate (FHR) patterns in the EFM and IA groups has not given any indication of significance for the Vintzileos trial. CONCLUSIONS: Our results lead to reconsidering the results of the Dublin trial and Vintzileos trial in terms of operational rates of births, hypothesizing that these results would have been significantly lower if FHR traces were interpreted using the current NICHHD guidelines, which aim to identify potential acidotic fetuses rather than hypoxic ones.

Age at menarche does not correlate with the endometriosis phenotype.

OBJECTIVE: To evaluate the association between the endometriosis phenotype and the age at menarche. DESIGN: An observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2). SETTING: Single university tertiary referral center. PATIENTS: To be eligible, women had to have undergone their 1st complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed the month before the surgery. Endometriotic lesions were classified into 3 phenotypes: superficial peritoneal endometriosis (SUP), endometrioma (OMA), or deep infiltrating endometriosis (DIE). Patients were divided into 3 groups: early menarche (< 12 years), typical menarche (≥ 12 and ≤ 13 years) and late menarche (> 13 years). The groups were compared in terms of general characteristics, medical history, disease phenotype, and disease severity. INTERVENTIONS: Surgical management for a benign gynecologic condition. MAIN OUTCOME MEASURE(S): Correlation between the endometriosis phenotype and the age at menarche. MEASUREMENTS AND MAIN RESULTS: From January 2004 to December 2016, 789 women with histologically confirmed endometriosis were enrolled in the study. The mean age at menarche was 12.9 ± 1.6 years of age, (range 9 to 18). The mean age at menarche and the mean time interval between menarche and the 1st surgery for endometriosis were not significantly different between the three phenotypes (SUP, OMA, DIE). When women with early menarche, typical menarche, or late menarche were compared, no differences were observed in terms of the endometriosis phenotype and the anatomical distribution of the endometriotic lesions. CONCLUSION: For women operated for the first time for endometriosis, age at menarche is not associated with the disease phenotype.

Evaluation of umbilical cord pulsatility after vaginal delivery in singleton pregnancies at term.

OBJECTIVES: To define the duration of umbilical cord pulsatility (UCP) after vaginal delivery and to evaluate its possible association with maternal characteristics and obstetric and neonatal variables. STUDY DESIGN: Prospective observational study on women with a singleton pregnancy at term who had a vaginal delivery and cord clamping at the cessation of pulsations. The collection of UCP duration was performed through a stopwatch and by manual palpation of the umbilical cord. Maternal (age, BMI, parity, antepartum hemoglobin), obstetric (pregnancy characteristics, gestational age at delivery, induction of labor, duration of the first, the second and the third stage of labor, post-partum blood loss, umbilical cord length) and neonatal (birthweight, Apgar score, hematocrit, hemoglobin) variables were then compared between two groups: long-term vs. short-term UCP. RESULTS: A total of 102 women were identified. The median duration of UCP after birth was 213 s (IQR 120, 420), corresponding to 3 min and 33 s. The long-term UCP group (n = 51) had a significantly longer duration of third stage of labor (median 12 vs. 8 min, p < 0.001) and a significantly higher birthweight (median 3530 g vs. 3250 g, p = 0.005) compared with the short-term UCP group (n = 51). No differences in the other variables were found between groups. CONCLUSION: For the first time we have reported the duration of UCP after vaginal delivery. An increased duration of UCP is associated with a prolonged duration of third stage of labor and a higher birthweight.

Peripartum and postpartum outcomes in uncomplicated term pregnancy following ART: a retrospective cohort study from two Italian obstetric units.

STUDY QUESTION: Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) have adverse peripartum and postpartum outcomes? SUMMARY ANSWER: Term pregnancies following ART, even if uncomplicated until birth, have a higher risk of retained placenta and postpartum hemorrhage (PPH). WHAT IS KNOWN ALREADY: There is consistent evidence that pregnancies following ART have higher incidence of complications during pregnancy. However, few studies specifically investigated birth outcomes in ART term pregnancies. STUDY DESIGN SIZE DURATION: A retrospective cohort study was conducted on 14 415 deliveries at two university tertiary care obstetric units. Clinical data were extracted by reviewing obstetric records of all deliveries from 1 January 2010 to 31 December 2014, in a standardized electronic database regarding the mother's health before and during pregnancy, complications during pregnancy and at birth, and neonatal outcome. PARTICIPANTS/MATERIALS SETTING METHODS: Following an accurate evaluation of exclusion criteria (multiparity, maternal pre-pregnancy diseases, prior uterine surgery, fetal malformations, intrauterine deaths, elective cesarean section and pregnancy complications), the group of uncomplicated singleton term pregnancies from autologous ART conception by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 188) was compared with a maternal age and body mass index (BMI) matched group of spontaneous pregnancies (n = 1168). Cases of intrauterine insemination (IUI) (n = 14) and ovulation induction with timed intercourse (n = 18) were not included. Labor, delivery and postpartum outcomes were evaluated. Odds ratios (OR) were adjusted with multivariable logistic regression to maternal age, BMI, nationality and gestational age at birth. MAIN RESULTS AND THE ROLE OF CHANCE: The age of women in the final analysis ranged from 25 to 45 years, while BMI ranged from 17 to 34 kg/m2. Uncomplicated term pregnancies with ART conception had a higher risk of operative delivery (adjusted OR 1.40, 95% confidence interval (CI) 1.01-1.95), retained placenta (adjusted OR 2.63, 95% CI 1.31-5.26) and PPH (adjusted OR 2.86 95% CI 1.37-5.99). Conversely, ART conception did not increase the risk of induced labor (adjusted OR 1.18, 95% CI 0.85-1.65). However, patients that conceived by ART and underwent labor induction had a higher risk of failed induction compared with the control group (adjusted OR 2.53, 95% CI 1.23-5.21). Infants born after ART had a similar birthweight, Apgar score and arterial blood pH compared with spontaneously-conceived ones. LIMITATIONS REASONS FOR CAUTION: The database lacked specific information about causes of infertility, smoking habit, family income and details on ART (fresh versus frozen cycle, IVF versus ICSI), limiting, in part, our analysis of the results. However, only autologous IVF/ICSI pregnancies were included in order to prevent bias related to conception by oocyte/embryo donation. In vivo conception ART cases were excluded because they were too few to allow comparison with IVF/ICSI. Nevertheless, the inclusion of only uncomplicated pregnancies provides a highly homogeneous and still representative population sample. Study sample is representative of a well-resourced obstetric facility in a high-income country, limiting to some extent the generalizability of study results. WIDER IMPLICATIONS OF THE FINDINGS: Pregnancies conceived by autologous ART that proceed uncomplicated until term may require counseling about the risk of placental retention with PPH. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest and funding to declare.

Twin pregnancies after assisted reproductive technologies: the role of maternal age on pregnancy outcome.

OBJECTIVES: Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART). STUDY DESIGN: The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165). RESULTS: Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%). CONCLUSIONS: Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Serum markers for the noninvasive diagnosis of endometriosis.

Endometriosis is a disease that affects millions of women worldwide and its diagnosis is still challenging. Medical history, symptoms together with imaging data may address the correct diagnosis, but the gold standard remains laparoscopic assessment with histological confirmation. The development of serum markers as diagnostic tools for endometriosis may allow a prompt and noninvasive diagnosis. Several serum biomarkers have been investigated over the years, but none of these have shown a clinical utility and nowadays the more realistic diagnostic biomarker consists in a panel of biomarkers. The recent introduction of new technologies such as genomics and proteomics may represent the future perspective of endometriosis diagnosis.

Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

Neuroendocrine and stress-related aspects of endometriosis.

Endometriosis is a model of a benign gynecologic disease associated with two major symptoms: pain and infertility. When becomes chronic, severe psychological and neuroendocrine changes may occur. The high levels of perceived stress caused by symptoms cause a neuroendocrine disequilibrium thus contributing to the progression of the disease. Elevated stress levels alter hormonal secretions, mood and behavior, sexual disorders and appetite custom. Inflammatory comorbidities may be associated with elevated stress in endometriotic patients (inflammatory bowel disease, fibromyalgia, chronic fatigue) and even autoimmune diseases (thyroid disease, systemic lupus erythematosus, multiple sclerosis). Neurogenic mechanisms are described in endometriotic lesions and they affect peripheral and central nervous system of these patients increasing pain sensitivity and stress reactivity. In conclusion, endometriosis is a disease which affects reproductive and neuroendocrine functions with a great impact on women's health and quality of life.

How to Manage Bowel Endometriosis: The ETIC Approach.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Endometriosis and perceived stress: impact of surgical and medical treatment.

BACKGROUND: The aim of the study was to investigate the levels of perceived stress in a group of women with a long-term history of endometriosis in conjunction with surgical and/or medical treatments. METHODS: A clinical trial was conducted at the Department of Molecular and Developmental Medicine, University of Siena, in collaboration with a non-profit association of women with endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of endometriosis (for at least 3 years) were included in this study. Each patient completed a semi-structured questionnaire and a validated scale to assess perceived stress, the Perceived Stress Scale (PSS) by e-mail. RESULTS: The study showed that in women with a long-term history of endometriosis, the level of perceived stress was increased by repeated surgical treatments and reduced by some medical treatments. The median PSS value was 23 (range 9-36) and 30.6% of the study population were included in the highest stress category (>26). The highest levels were found in patients who had undergone the most surgery. The use of progestins was associated with a lower perceived stress (p = 0.004) than in the patients treated with gonadotropin-releasing hormones. CONCLUSIONS: Long-term endometriosis has a relevant impact on perceived stress, in particular in those undergoing repeated surgery.

Preoperative and Postoperative Clinical and Transvaginal Ultrasound Findings of Adenomyosis in Patients With Deep Infiltrating Endometriosis.

OBJECTIVES: Deep infiltrating endometriosis (DIE) represents the most complex form of endometriosis and its treatment is still challenging. The coexistence of DIE with other appearances of endometriosis stimulates new studies to improve the preoperative diagnosis. Adenomyosis is a clinical form that shares several symptoms with DIE. The present study investigated the possible presence of adenomyosis in a group of women with DIE and its impact on pre- and postoperative symptoms. MATERIALS AND METHODS: A group of women (n = 121) undergoing laparoscopic treatment for DIE were enrolled. Clinical and ultrasound evaluations were performed as preoperative assessment. The ultrasonographical appearances of DIE and of adenomyosis were recorded by 2-dimensional ultrasound. The following symptoms were considered: dysmenorrhea, dyspareunia, abnormal uterine bleeding, bowel, and urinary symptoms. Pain was evaluated by the visual analog scale system and menstrual bleeding was assessed by the use of the pictorial blood assessment chart. In a subgroup of women (n = 55), a follow-up evaluation (3-6 months after surgery) was done. RESULTS: A relevant number of patients with DIE showed adenomyosis (n = 59; 48.7%); in this group, dysmenorrhea (P = .0019), dyspareunia (P = .0004), and abnormal uterine bleeding (P < .001) were statistically higher than that in the group with only DIE. After surgery, painful symptoms improved in the whole group but remained significantly higher (P < .001) in the group with adenomyosis. CONCLUSIONS: Deep infiltrating endometriosis is frequently associated with adenomyosis, significantly affecting pre- and postoperative symptoms and thus influencing the follow-up management.

Uterine fibroids affect pregnancy outcome in women over 30 years old: role of other risk factors.

OBJECTIVE: To evaluate the pregnancy outcome in women >30 years old with uterine fibroids also considering other possible concomitant risk factors. METHODS: A multicentric, observational and retrospective study was conducted. All women were asked to complete a questionnaire while they were in hospital and the outcome of pregnancy was investigated. RESULTS: Women with uterine fibroids before pregnancy were more frequently >35 years old and in their clinical history before pregnancy showed more pelvic pain, polliachiuria, previous pelvic surgery, hypermenorrhea and dysmenorrhea, than control women (p < 0.0001). During pregnancy patients with uterine fibroids showed significantly more threatened preterm birth (PTB) and PTB, weight gain, hyperemesis, gestational hypertension and post-partum bleeding and showed more often requirement for emergency cesarean section (p < 0.0001). The multivariate logistic regression model used for evaluating the effect of clinical parameters on outcome of pregnancy showed that age >35 years, pelvic pain, work, weight gain, hyperemesis, threatened miscarriage and threatened PTB were significantly correlated with unfavorable pregnancy outcome , independently of the presence of uterine fibroids (p < 0.0001). CONCLUSIONS: The present study confirming a more frequent negative pregnancy outcome in presence of uterine fibroids, showed that other risk factors may affect pregnancy and delivery outcome in women aging >30 years old.

Activins and related proteins in the establishment of pregnancy.

Activin A and related proteins (inhibins, follistatin [FS], follistatin-related gene [FLRG], endometrial bleeding associated factors [ebaf]) are involved in the complex mechanisms allowing the establishment and the maintenance of pregnancy. As a consequence of ovarian progesterone stimuli, activin A is expressed and secreted by the stromal endometrial cells, which locally induces the decidualization process, a prerequisite for implantation. Moreover, activin A does influence the implantation phase, also enhancing cytotrophoblast differentiation, indirectly, by increasing the expression of other molecules involved in embryo implantation, such as matrix metalloproteinases (MMPs) and leukemia inhibitory factor (LIF). The local derangement of activin A pathway in some pregnancy disorders (incomplete and complete miscarriages, recurrent abortion, and ectopic pregnancy [EP]) further sustains the hypothesis that activin A and its related proteins play a relevant role in the establishment of pregnancy.

Activin A in asphyxiated full-term newborns with hypoxic ischemic encephalopathy.

Activin-A is a protein over-expressed and secreted by the brain after neuronal destruction. We evaluated whether serum activin-A increases in asphyxiated full-term newborns (AFTNs) at risk of hypoxic-ischemic-encephalopathy (HIE). 105 consecutive infants (35 affected by perinatal asphyxia due to acute fetal distress; 70 healthy gestational-age matched newborns) underwent cranial assessment and neurologic examination at 12, 24 and 72 hours after birth and, on discharge from the hospital and; activin-A and monitoring laboratory variables assessment at birth. According to the occurrence of HIE within 7-days after birth, AFTNs were subdivided in Group A (n= 20; no/mild HIE with good prognosis) and Group B (n= 15; moderate/severe HIE with a greater risk of neurological handicap). Activin-A was significantly (P less than 0.0001) higher in Groups A and B than controls and highest (P less than 0.001) in Group B. At 0.66 ng/L activin-A achieved a sensitivity of 93.33 per cent and a specificity of 96.63 per cent, respectively, as HIE diagnostic test. These findings show that activin A increased in AFTNs with HIE before the appearance of related signs.

S100B protein and near infrared spectroscopy in preterm and term newborns.

Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants although data in healthy infants are lacking. The present study investigates whether NIRS parameters change according to gestational age and correlate with S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in which we performed in the first 6-hours after birth routine clinical, radiological and laboratory variables, cerebral oxygen saturation (rSO2), fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than 0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39 weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77; FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that NIRS parameters and S100B protein correlation may be of help in brain function monitoring.

Biochemical markers of perinatal brain damage.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia. To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, S100B, activin A, neuronal specific enolase (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia.

Urinary S100A1B and S100BB to predict hypoxic ischemic encephalopathy at term.

Urinary S100A1B and S100BB were measured to detect cases at risk of hypoxic-ischemic encephalopathy (HIE) in asphyxiated newborns. We recruited 42 asphyxiated infants and 63 healthy term neonates. S100A1B and S100BB were measured at first urination (time 0) and at 4 (time 1), 8 (time 2), 12 (time 3), 16 (time 4), 20 (time 5), 24 (time 6), 72 (time 7) hours after birth. 20 infants had no/mild HIE with good prognosis (Group A) and 22 had moderate/severe HIE with a greater risk of neurological handicap (Group B). Urine S100A1B and S100BB levels were significantly (P less than 0.0.01, for all) higher at all monitoring time-points in Group B than Group A and controls, but not between Group A and controls. Both S100A1B and S100BB have great sensitivity and specificity for HIE since their first measurement. In conclusion, S100A1B and S100BB are increased in urine collected from asphyxiated newborns who will develop HIE since first urination, and their measurement may be useful to early predict HIE when monitoring procedures are still of no avail.