Ursodeoxycholic acid in the treatment of pregnancy cholestasis: a data-set available for Meta-analyses.

BACKGROUND: The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses. AIM: Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses. METHODS: Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 µmol/L) and high-level bile acid (at least 40 µmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially. CONCLUSION: The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

Perspectives of Italian pregnant women on pregnancy examinations and pregnancy care: is the caregiver more important than the care?

AIM: Assessing awareness of Italian low-risk pregnant patients on low-risk pregnancy care and what do they feel about their own pregnancy. METHODS: A questionnaire was administered to 382 low-risk pregnant women. This questionnaire assessed general knowledge of low-risk pregnancy, low-risk pregnancy care, and how much patients rated ten topics of low-risk pregnancy care. It would be expected that the knowledge of each topic would associates with the patient's perceived importance of that topic. RESULTS: Poor knowledge of pregnancy care was proven. Patients seem to incorrectly overrate vaginal examinations and obstetric and gynecologist-led care, while they attribute appropriate importance to midwife-led care. The more examinations performed (vaginal examinations, sonographic checks, cardiotocographies), the higher their rating. CONCLUSIONS: In Italy, expectations of pregnant women about their own pregnancy are incorrectly trusted in the obstetrics and gynecologists. Both poor knowledge of pregnancy care and cultural perspectives on the birth process amongst Italian people explain the finding. Referring low-risk pregnant women to midwives would help them to rate more the care than the caregiver.

Effect of corticosteroids and progesterone on adrenomedullin output and expression in human fetal membranes and placenta trophoblasts.

OBJECTIVE: Plasma adrenomedullin (AM) concentrations are increased in fetal and maternal circulation in response to exogenous glucocorticoids administration. The role of corticosteroids and progesterone in regulating AM synthesis and secretion was investigated in amnion and chorion trophoblast cells of the fetal membranes and in placental trophoblast cells. STUDY DESIGN: Cells were treated with betamethasone, hydrocortisone, and progesterone. Changes in AM output were measured with radioimmunoassay. Protein expression was evaluated with Western blot and immunohistochemistry. RESULTS: Betamethasone stimulated AM secretion and protein expression in placental trophoblast cells and in amnion cells of the fetal membranes. Hydrocortisone and progesterone did not induce any effect either on secretion or protein expression in placenta and fetal membranes cells. CONCLUSION: Glucocorticoids regulate AM secretion and expression by human placenta thereby promoting increased AM concentration in maternal and fetal circulation in circumstances characterized by increased cortisol levels.

Intrafollicular concentration of adrenomedullin is associated with IVF outcome.

OBJECTIVE: To test the hypothesis that serum or intrafollicular concentrations of adrenomedullin (AM) would correlate with reproductive outcomes in in vitro fertilisation (IVF) cycles. DESIGN: Serum and follicular fluid samples were collected during transvaginal oocyte retrieval. The follicular fluid was individually aspirated, and the presence of oocyte was recorded. AM concentrations were measured using an enzyme-linked immunosorbent assay. SETTING: Department of Gynaecology, Perinatology and Child Health, 'Sapienza' University of Rome, Italy. PATIENTS: Eighty women undergoing IVF for primary infertility aged 18-45 years. MAIN OUTCOME MEASURES: AM concentrations in plasma and follicular fluid were correlated to follicular fluid volume, presence of oocyte, oocyte maturation, embryo grading, fertilisation and pregnancy rates, live-birth rate and plasma estrogen concentration. RESULTS: Monofollicular fluid AM concentrations did not differ between follicles containing oocyte and those without oocyte; however, AM concentrations were lower in follicles that resulted in pregnancy than in those that failed. Serum but not follicular fluid AM concentrations correlated with serum estrogen levels. Follicular fluid AM correlated with plasma AM levels. CONCLUSION: We conclude that higher level of AM in the follicular fluid appears to be associated with a negative outcome in IVF treatment.

Cesarean section in the absence of labor and risk of respiratory complications in newborns: a case-control study.

AIM: To establish if labor and gestational age have an additive effect on the likelihood of newborn respiratory complications. METHODS: Case-control study on singleton pregnancies, delivered between 34 and 41 weeks. Cases were collected among newborns discharged with diagnoses of respiratory complications, as codified by ICD 9 1997. Subsequently, pneumonias, meconium aspiration syndromes, and pulmonary hemorrhage were excluded. Controls were all other newborns without respiratory complications. Multivariate analyses were performed hypothesizing and not hypothesizing a relationship between gestational age, labor and newborn adverse respiratory outcomes. RESULTS: Twenty thousand three hundred and ninety-seven living babies born at term or near-term between January 2006 and December 2010 were assessed. 16,084 infants were included in the analyses. 304 experienced a respiratory complication (cases group). Delivering by cesarean not in labor increases the odds ratio of adverse respiratory outcome by about 2, independently from other variables, among which is gestational age. The same increase of odds ratio of 2 is constantly observed at each week of gestation, from 35 to 39 gestational weeks. CONCLUSIONS: Cesarean not in labor adds a constant risk of newborn respiratory complications at any gestational age near-term and early-term. The more the planned cesarean is delayed, the better is newborn respiratory outcome.

Effects of prenatal betamethasone administration on leptin and adiponectin concentrations in maternal and fetal circulation.

OBJECTIVE: The aim of this study was to determine the effects of in vivo administration of prenatal betamethasone on leptin and adiponectin concentration in maternal and fetal circulation. STUDY DESIGN: Blood samples were collected from 35 pregnant women receiving betamethasone for threatened preterm delivery before and at different time points after drug administration. Cord blood was collected at delivery in infants born from mothers treated with betamethasone and in 15 infants who delivered at the same gestational age not receiving betamethasone. RESULTS: Betamethasone caused an approximately 170% increase in maternal leptin at 24 hours after betamethasone, whereas it had no effects on adiponectin concentration. Betamethasone affects neonatal leptin and adiponectin levels in a time-dependent manner. The glucocorticoid-induced changes in the relationship between these adipokines in maternal and fetal circulation was long lasting. CONCLUSION: These results provide the first evidence for in vivo effects of glucocorticoids on maternal and fetal adipokines relationship in human pregnancy.

Effect of calcium ionophore A23187 on prostaglandin synthase type 2 and 15-hydroxy-prostaglandin dehydrogenase expression in human chorion trophoblast cells.

OBJECTIVE: Prostaglandins induce parturition in humans. Prostaglandin output is regulated by the synthetic and metabolic enzymes, prostaglandin synthase type 2 (PTGS2) and 15-hydroxyprostaglandin dehydrogenase (PGDH). The role of calcium in regulating PTGS2 and PGDH expression was investigated in chorion trophoblasts. STUDY DESIGN: Cells were treated with calcium ionophore A23187 in the presence or absence of calcium chelators; changes in messenger ribonucleic acid expression were measured with real-time polymerase chain reaction and analyzed with analysis of variance. Protein expression was evaluated with Western blot and dual immunofluorescence. RESULTS: A23187 stimulated PTGS2 and suppressed PGDH expression. Effects of A23187 were reversed by calcium chelators. PTGS2 had perinuclear and cytosolic distribution, whereas PGDH was cytosolic. Some cells expressed both enzymes, some neither enzyme, and some either PTGS2 or PGDH. CONCLUSION: Chorion cells showed heterogeneity in the expression of PTGS2 and PGDH. Calcium influx regulates PTGS2 and PGDH expression, thereby promoting coordinated increased prostaglandin output in circumstances such as term and preterm labor.

Risk factors for fatality in amniotic fluid embolism: a systematic review and analysis of a data pool.

PURPOSE: Investigating risk factors for amniotic fluid embolism (AFE)-induced fatality. METHODS: A systematic review of cases of AFE available on PubMed, Scielo, Scopus and AJOL databases that occurred from 1990 to 2015 was carried out. After careful reading of titles, abstracts and full texts, case reports of AFE were reviewed. Risk factors for AFE were considered as independent variables in logistic regression models. The first model was built on the whole data pool. The second model was built on typical cases of AFE, according to the classical triad of symptoms (heart, lungs, coagulopathy). The dependent variable was fatality in both models. RESULTS: 177 cases of AFE were assessed in the first model, while 121 typical cases of AFE were assessed in the second model. Among typical cases of AFE, only oxytocin infusion during labour increases the likelihood of death (odds ratio 2.890, 95% confidence interval 1.166-7.164, p = 0.022). No risk factors for fatality were found in the whole data pool. CONCLUSIONS: Further research on national registries should focus on the behaviour of oxytocin infusion during labour in AFE cases.

The level of adrenomedullin immunoreactivity in seminal fluid is higher in oligozoospermic subjects and correlates with semen biochemical parameters.

OBJECTIVE: The newly discovered vasoactive peptide, adrenomedullin, and its receptors are widely distributed in various non-vascular tissues. Recent studies have suggested the possible regulatory role of adrenomedullin (AM) at several levels of the pituitary-gonadal axis. We determined the level of adrenomedullin-like immunoreactivity in the seminal fluid and examined its possible correlation with routine semen parameters, semen biochemical levels or plasma levels of FSH, LH, testosterone or prolactin. MATERIALS AND METHODS: A total of 51 males were divided into three groups according to semen analysis: (i) normospermic (n=19); (ii) oligozoospermic (n=17); (iii) azoospermic (n=15). All the subjects were submitted to hormone analysis (LH, FSH, testosterone, prolactin), routine semen parameters and semen biochemical levels (fructosio, citric acid, L-carnitine, nitric oxide) evaluation. AM was determined in plasma and seminal fluid using a specific radioimmunoassay. RESULTS: Mean AM concentration in seminal plasma was higher in oligozoospermic subjects than in normospermic males. In patients with non-obstructive azoospermia AM in semen was significantly lower than in patients with obstructive azoospermia. Semen AM levels correlated negatively with citric acid concentrations in oligozoospermic subjects. In patients with obstructive azoospermia AM in seminal fluid was correlated with citric acid levels. There was a relationship between plasma AM and prolactin. CONCLUSIONS: We conclude that in human seminal fluid AM concentration is increased in infertile oligozoospermic patients and derives very likely from the prostate. Its role in the regulation of male fertility, however has to be understood.

Localization and distribution of adrenomedullin receptor in the human placenta: changes with gestational age.

OBJECTIVE: To examine the distribution and localization of adrenomedullin (AM) receptor (AM-R) in human placenta and fetal membranes to assess any change during pregnancy or with labor. STUDY DESIGN: Immunohistochemistry was performed by the avidin/biotin immunoperoxidase method using an antibody specific to AM-R on intrauterine tissues collected from 7-41 weeks of gestation (n=73). RESULTS: AM-R was localized in the placenta and fetal membranes in all 3 trimesters. The distribution of AM-R in the villous and extravillous trophoblast cells of the placenta and in chorion and decidua cells of the fetal membranes changed with gestational age but not with labor. CONCLUSION: AM is secreted by decidua and trophoblast cells that also possess AM-R, suggesting that placental tissues function in both the synthesis and action of AM. Changes in AM-R in the placenta during pregnancy may reflect changes in AM function throughout gestation.

Metastatic pancreatic cancer in late pregnancy: a case report and review of the literature.

The occurrence of pancreatic carcinoma in a young patient is rare and even more so in pregnancy. In this case report, we discuss the presentation and management of pancreatic adenocarcinoma, with lung and liver metastases, diagnosed in a woman in her third trimester of pregnancy (28 weeks). Ultrasound and magnetic resonance imaging scans were carried out and pancreatic mass biopsy during endoscopic retrograde cholangiopancreatography was performed. Severe preeclampsia and fetal growth restriction occurred. A female infant was delivered by cesarean section at 30 weeks of gestation for worsening of maternal clinical conditions and hepatic and pancreatic tests. The patient died 50 days after delivery. Although pancreatic cancer is a very rare event in pregnancy, it should be suspected when epigastric abdominal pain and laboratory parameters suggestive of biliary tract obstruction occur in pregnancy to ensure, at the least, a better pregnancy outcome.

Symphysis-fundal height predicts difficult evolution of induced labours.

BACKGROUND AND AIM: Symphysis-fundal-height (SFH) could be prove useful for the management of labour. This study aims to assess the behaviour of induced labours in relationship with SFH values. METHODS: Prospective observational study in a sample of 158 women underwent induction with intravaginal dinoprostone for different indications. SFH, SFH corrected for station, gestational age and parity were considered independent variables in multivariable models. Vaginal delivery, operative vaginal delivery, Cesarean section, Cesarean section for dystocia, Cesarean section for cardiotochographyc abnormalities, oxytocin infusion (for potentiating labour), need of Kristeller's maneuvre, epidural anesthesia (on demand), episiotomy, time from the first dose of dinoprostone to delivery, and time of active phase of labour were considered dependent variables in multivariable models. RESULTS: SFH >34 cm (both uncorrected and corrected for station) independently associates with an increase of odds ratio for operative vaginal birth, Kristeller's maneuver, oxytocin use, episiotomy. Additionally, SFH >34 cm (corrected for station) seems to correlate with increasing time of active phase of labour. CONCLUSIONS: SFH >34 cm (both corrected and uncorrected for station) predicts difficult vaginal deliveries and operative vaginal deliveries in induced labours.

Adrenomedullin in human male reproductive system.

OBJECTIVE: To investigate adrenomedullin (AM) localization and distribution in human male reproductive system and to determine whether seminal fluid AM concentration correlates with sperm parameters. STUDY DESIGN: Plasma and semen samples (n = 19) obtained from healthy volunteers with normal seminal fluid parameters were assayed for AM using a specific RIA. AM immunostaining was sought on sections of penile cavernous bodies and testicular tissues obtained postmortem from four young males after accidental death using a polyclonal antibody to AM 1-52. RESULTS: Mean AM concentration in seminal plasma was 209.4+/-46.6 pg/ml, 8-9-fold higher than in circulating plasma and correlated with sperm motility (r = 0.715, p < 0.01). Endothelial cells of cavernous vessels stained for AM. Intense AM immunostaining was found in germinal cells and in peritubular myocytes and Leydig cells in the testis. CONCLUSIONS: These findings demonstrated for the first time that AM is localized in human male reproductive system. The local secretion of AM suggests that AM may contribute either in the penile erection and in the regulation of testicular function and sperm motility.

Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study.

BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

Measurement of urinary S100B protein concentrations for the early identification of brain damage in asphyxiated full-term infants.

BACKGROUND: Perinatal asphyxia is a major cause of mortality and morbidity. To date there are no reliable methods to detect which infants will develop brain damage after asphyxia insult. We investigated whether measurements of urine levels of S100B in asphyxiated full-term newborns may be a useful tool for early detection of postasphyxia brain damage. METHODS: A prospective study of 38 infants with perinatal asphyxia and 96 control subjects, recruited at 3 tertiary departments of neonatology between April 1, 1999, and July 31, 2001. Routine laboratory variables, neurologic patterns, and urine concentrations of S100B protein were determined at 4 predetermined time points (first urination and 12, 24, and 72 hours after birth). The concentrations of S100B protein in urine were measured using an immunoluminometric assay. The results were correlated with the presence or absence of neurologic abnormalities at age 12 months. RESULTS: S100B protein levels were significantly higher in samples collected at all monitoring times from new-borns with abnormal neurologic findings on follow-up (first urination, 1.92 +/- 0.33 micro g/L; 12 hours, 2.78 +/- 1.71 micro g/L; 24 hours, 4.75 +/- 4.08 micro g/L; 72 hours, 5.93 +/- 1.63 micro g/L) than in samples from those without (first urination, 0.24 +/- 0.06 micro g/L; 12 hours, 0.13 +/- 0.06 micro g/L; 24 hours, 0.21 +/- 0.07 micro g/L; 72 hours, 0.12 +/- 0.04 micro g/L) or from healthy infants (first urination, 0.11 +/- 0.01 micro g/L; 12 hours, 0.12 +/- 0.03 micro g/L; 24 hours, 0.12 +/- 0.02 micro g/L; 72 hours, 0.12 +/- 0.02 micro g/L) (P<.001 for all). An S100B concentration cutoff of 0.28 micro g/L at first urination had a sensitivity of 100% and a specificity of 87.3% for predicting the development of abnormal neurologic findings on follow-up. The sensitivity and specificity of measurements obtained between 12 and 72 hours were up to 100% and 98.2%, respectively. CONCLUSION: Longitudinal S100B protein measurements in urine soon after birth are a useful tool to identify which asphyxiated infants are at risk of long-term neurologic sequelae.

Ontogenetic localization and distribution of S-100beta protein in human placental tissues.

OBJECTIVE: To investigate whether S-100beta, a brain-specific protein found in amniotic fluid and fetal circulation, is present in fetoplacental tissues throughout gestation. METHODS: S-100beta protein localization and concentration were assessed in placentae, fetal membranes, and cord vessels. Tissues were obtained from 40 pregnant women at different gestational ages: first trimester (n = 10), second trimester (n = 10), early third trimester (n = 10), and late third trimester (n = 10). RESULTS: In the placenta, S-100beta was localized in villous and intermediate trophoblast cells. The intensity of immunostaining and protein concentration increased with advancing gestation. S-100beta protein was also present in amnion, trophoblast, and decidual cells of fetal membranes, and in endothelial cells of umbilical vessels at all gestational ages. CONCLUSION: This study demonstrated that fetoplacental tissues contain S-100beta protein, suggesting that these tissues may, at least in part, be responsible for the high level found in the fetal circulation. Although the significance of placental S-100beta is unknown, this origin should be taken into account when this protein is used as a marker of brain injury in the fetus or infant at birth.

Adrenomedullin in perinatal medicine.

This review will consider whether adrenomedullin (AM) plays a role in the different aspects of perinatal medicine: contributing to maternal systemic vasodilatation during pregnancy, regulating uterine and placental blood flow, being involved in the process of implantation and participating in uterine quiescence prior to parturition. In addition, this will also consider whether a modification of AM secretion contributes to some pathological conditions in pregnancy such as preeclampsia and impairment of fetal growth. The biosynthesis of AM increases in gravid rats and in pregnant women, and the placenta represents an important site of AM production during pregnancy. Both the peptide and its receptors have been found in the uterus, placenta, fetal membranes and cord vessels, and fetal membranes and placental tissues in culture secrete AM. AM contributes to maternal systemic vasodilatation, the placental vessels are relaxed by AM in a dose-dependent manner and AM is expressed in the fetoplacental and umbilical vascular endothelium where basal production of AM contributes to low fetoplacental vascular resistances. Controversy exists over the status of circulating and placental AM in preeclampsia and of the relative contribution of AM to impaired fetoplacental circulation and fetal growth. Moreover, the uterus expresses AM mRNA and exogenous AM relaxes the myometrium in a dose-dependent manner; however, clinical studies have shown that AM does not decrease before the onset of parturition. Rather, AM secretion increases during spontaneous labor and in preterm delivery.

Follicular fluid adrenomedullin concentrations in spontaneous and stimulated cycles: relationship to ovarian function and endothelin-1 and nitric oxide.

The objective of this study was to determine concentration of adrenomedullin (AM) in follicular fluid and whether a correlation exists between AM and nitric oxide (NO) or endothelin-1 (ET-1) levels in follicular fluid, serum 17beta-estradiol or other parameters of ovarian function in spontaneous and gonadotrophin stimulated ovarian cycles. Follicular fluid samples were obtained at oocyte retrieval from 50 women who underwent an in vitro fertilization (IVF) program: 40 undergoing ovarian hyperstimulation with recombinant FSH and 10 had spontaneous ovarian cycles. AM, ET-1, and NO were detected in all of the follicular fluid samples and their concentrations were similar in spontaneous and stimulated cycles. In patients undergoing ovarian stimulation, follicular fluid AM levels correlated with serum 17beta-estradiol concentration. No correlation was found between follicular AM concentration and parameters of ovarian function. Similarly, no relationship was observed between ET-1, NO, and AM follicular fluid concentrations in either spontaneous or stimulated cycles. This study suggests a possible regulatory effect of the sexual hormones on AM production by the ovary during the ovulatory process. The site of AM secretion and its function (if any), however, remain to be established.

Adrenomedullin increases in term asphyxiated newborns developing intraventricular hemorrhage.

OBJECTIVES: Adrenomedullin (AM) is a newly discovered vasodilator peptide that participates in the regulation of cerebral blood flow. The aim of this study was to investigate whether circulating AM was increased in infants with prenatal asphyxia who developed intraventricular hemorrhage (IVH). DESIGN AND METHOD: : A case-control study was performed on 40 full-term asphyxiated newborns: 20 developed IVH (group A) and 20 did not (group B). Forty term healthy newborns represented the control group. Biochemical laboratory parameters, neurological patterns, cerebral ultrasound scanning, and Doppler velocimetry were assessed at 12 and 72 h from birth. Plasma AM concentration was measured at 12 h from birth by means of a specific RIA. RESULTS: AM levels were significantly higher in group A (20.2 +/- 5.2 fmol/ml) than in group B (8.4 +/- 2.1 fmol/ml) or controls (9.3 +/- 2.6 fmol/ml). In asphyxiated newborns, AM concentration was correlated with middle cerebral artery PI value only in group B. CONCLUSIONS: Increased concentration of AM at 12 h from birth in asphyxiated newborns who later developed IVH suggests that this peptide may participate in the loss of cerebral vascular autoregulation in response to hypoxia and could be useful to discriminate, among newborns at risk, those with an adverse neurological outcome.