Papers by Filiberto M. Severi
Management and Therapy of Late Pregnancy Complications, 2017
Cells
Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effect... more Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effects or impediments. Pregnancy is generally accepted as a period of well-being in which relapses have a softer evolution, particularly in the third trimester. Herein, we hypothesized that the placenta, via its “secretome”, could contribute to the recognized beneficial effects of pregnancy on MS activity. We focused on a well-known receptor/ligand/decoy receptor system, such as the one composed by the receptor activator of nuclear factor-kB (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG), which have never been investigated in an integrated way in MS, pregnancy, and placenta. We reported that pregnancy at the term of gestation influences the balance between circulating RANKL and its endogenous inhibitor OPG in MS women. We demonstrated that the placenta at term is an invaluable source of homodimeric OPG. By functional studies on astrocytes, we showed that placental OP...
Cells
Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effect... more Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effects or impediments. Pregnancy is generally accepted as a period of well-being in which relapses have a softer evolution, particularly in the third trimester. Herein, we hypothesized that the placenta, via its “secretome”, could contribute to the recognized beneficial effects of pregnancy on MS activity. We focused on a well-known receptor/ligand/decoy receptor system, such as the one composed by the receptor activator of nuclear factor-kB (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG), which have never been investigated in an integrated way in MS, pregnancy, and placenta. We reported that pregnancy at the term of gestation influences the balance between circulating RANKL and its endogenous inhibitor OPG in MS women. We demonstrated that the placenta at term is an invaluable source of homodimeric OPG. By functional studies on astrocytes, we showed that placental OP...
Journal of Perinatal Medicine, 2005
Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation ... more Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation to vibroacoustic stimulation in healthy preterm fetuses. Materials and methods: A total of 22 women with uncomplicated pregnancies at 30-34 weeks participated in the study. Vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal head for a period of 2 s every 10 s. Fetal eye tightening monitored by ultrasound within 2 s of the stimulus was considered a positive response. The habituation rate was defined as the number of stimuli applied before the fetus stopped responding to two consecutive stimuli. Results were compared using the Mann-Whitney U-test. Results: All 22 fetuses showed habituation at a rate that varied from 1 to 9 (mean 4.2"1.8). Conclusion: BSR is a good marker of habituation in preterm fetuses. Further study is needed to ascertain whether abnormal BSR habituation could be a sign of fetal distress.
Journal of Perinatal Medicine, 2005
Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation ... more Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation to vibroacoustic stimulation in healthy preterm fetuses. Materials and methods: A total of 22 women with uncomplicated pregnancies at 30-34 weeks participated in the study. Vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal head for a period of 2 s every 10 s. Fetal eye tightening monitored by ultrasound within 2 s of the stimulus was considered a positive response. The habituation rate was defined as the number of stimuli applied before the fetus stopped responding to two consecutive stimuli. Results were compared using the Mann-Whitney U-test. Results: All 22 fetuses showed habituation at a rate that varied from 1 to 9 (mean 4.2"1.8). Conclusion: BSR is a good marker of habituation in preterm fetuses. Further study is needed to ascertain whether abnormal BSR habituation could be a sign of fetal distress.
Journal of Perinatal Medicine, 2005
Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation ... more Objective: To investigate whether the blink-startle reflex (BSR) is a good marker of habituation to vibroacoustic stimulation in healthy preterm fetuses. Materials and methods: A total of 22 women with uncomplicated pregnancies at 30-34 weeks participated in the study. Vibroacoustic stimulus was repeatedly applied to the maternal abdomen above the fetal head for a period of 2 s every 10 s. Fetal eye tightening monitored by ultrasound within 2 s of the stimulus was considered a positive response. The habituation rate was defined as the number of stimuli applied before the fetus stopped responding to two consecutive stimuli. Results were compared using the Mann-Whitney U-test. Results: All 22 fetuses showed habituation at a rate that varied from 1 to 9 (mean 4.2"1.8). Conclusion: BSR is a good marker of habituation in preterm fetuses. Further study is needed to ascertain whether abnormal BSR habituation could be a sign of fetal distress.
The Journal of Clinical Endocrinology & Metabolism, 2011
Context: Investigation of activin-A (A) and myostatin (M) in human myometrium (HM) and leiomyoma ... more Context: Investigation of activin-A (A) and myostatin (M) in human myometrium (HM) and leiomyoma (HL) will explain their involvement in human myometrial pathophysiology. Objective: We aimed to investigate A and M response and steroid regulation in HM. We also evaluated A and M expression and response in HL. Design: Tissues were analyzed and cultured. Patients: Patients included fertile (in proliferative phase) and menopausal women undergoing hysterectomy. Interventions: HM explant cultures were treated with A and M (for Smad-7 mRNA quantification) or estrogen and progesterone (for A and M mRNA quantification). A and M expression levels were also evaluated in menopausal (physiological absence of steroids) HM specimens. A and M and their receptors were evaluated in HL (n ϭ 8, diameter 5-8 cm) compared with their matched HM. HL explants cultures were treated with A and M (for Smad7 mRNA quantification), and, to explain the absence of response, the levels of follistatin, follistatin-related gene (FLRG), and Cripto were evaluated. Results: A and M increased Smad7 expression in HM explants. A and M mRNAs were both reduced after estradiol treatment, unchanged after progesterone treatment, but were higher in menopausal than fertile (in proliferative phase) specimens. A, M, and FLRG were expressed at higher levels in HL compared with adjacent HM, whereas the receptors, follistatin, and Smad7 mRNAs resulted unchanged. Cripto mRNA was expressed only in HL.
American Journal of Obstetrics and Gynecology, 2008
To evaluate the clinical efficacy and safety of vaginal prostaglandin (PGE2) insert in cervical r... more To evaluate the clinical efficacy and safety of vaginal prostaglandin (PGE2) insert in cervical ripening and induction of labor in various clinical conditions. STUDY DESIGN: A retrospective study including 241 pregnant women who received dinoprostone by vaginal slow release insert for cervical ripening and induction of labor. The treatment was given for: post-term pregnancy (67%), oligohydramnios (11%), gestational hypertension (8.2%), fetal growth restriction (4.5%), and suspected fetal macrosomia (2.5%). The potential prognostic factors evaluated were: maternal age, parity, gestational age, bishop score. The main outcome measure was induction-delivery interval; secondary outcomes were the number of PGE2 applications needed and the application-ripening interval. Data were analyzed by chi-square test with continuity correction and Cox regression. RESULTS: The majority of the patients (nϭ160, 67%) went into active labor within 24 h from the vaginal insert, with a subgroup of 30% (nϭ71) in whom the time was Ͻ12 h. The mean time for cervical ripening was 21 h and the mean time to delivery was 26 h. Failure of cervical ripening occurred in 34 cases of 241 (14%), and was not related to gestational age (2 ϭ0.29; p-valueϭ0.59) or parity (2 ϭ1.75; p-valueϭ0.18). The induction-to-delivery interval was significantly related to the parity: 61% of nulliparous versus 88.4% of the non-nulliparous delivered within 24h. This difference was confirmed by survival analysis, including Cox regression with adjustment for gestational age, Bishop score and maternal age. Sixty women delivered by cesarean section, of whom 35 were justified by abnormal fetal heart rate and only 4 cases of Apgar score Ͻ7. CONCLUSION: The observation of this large series of consecutive patients suggests that the use of a vaginal slow release dinoprostone insert for labor induction is highly efficacious and with limited side effects. Parity is the only independent factor to predict induction-delivery interval.
American Journal of Obstetrics and Gynecology, 2008
American Journal of Obstetrics and Gynecology, 2008
Global Imaging Insights, 2017
Human Reproduction Open
Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) h... more 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/m 2. 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.
The Journal of Maternal-Fetal & Neonatal Medicine
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016
associated cystocele and ten (40.0%) had associated rectocele; ten (40.0%) had urinary incontinen... more associated cystocele and ten (40.0%) had associated rectocele; ten (40.0%) had urinary incontinence. The mean operative time was 73.4 min (range 21-128 min); additional procedures were performed in twelve cases (70.6%). Anatomical success was achieved in all cases. There were no intraoperative complications. The postoperative complications were two cases (8.0%) of fever, and one case (4.0%) of hemorrhage (without transfusion). The mean time of hospitalization was 2.7 days (range 1-5). The mean follow-up time was 17.2 months (range 2-96 months). No relapse occurred. Currently there is a case of successful pregnancy ongoing. Conclusion: Manchester operation is an effective procedure with low rate of complications and should be considered a surgical option that allows preservation of the uterus.
Human Reproduction Update, 2017
bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongf... more bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongful birth and wrongful life. A review of the international state of law was carried out, focusing attention on the peculiar issue of wrongful life and investigating the different jurisdictional solutions of wrongful life claims in a comparative survey. OUTCOMES: Courts around the world are generally reluctant to acknowledge wrongful life claims due to their ethical and legal implications, such as existence as an injury, the right not to be born, the nature of the harm suffered and non-existence as an alternative to a disabled life. Most countries have rejected such actions while at the same time approving those for wrongful birth. Some countries, such as France with a law passed in March 2002, have definitively excluded Wrongful Life action. Only in the Netherlands and in three states of the USA (California, Washington and New Jersey) are Wrongful Life actions allowed. In other countries, such as Belgium, legislation is unclear because, despite a first decision of the Court allowing Wrongful Life action, the case is still in progress. There is a complete lack of case law regarding wrongful conception, wrongful birth and wrongful life in a few countries, such as Estonia. WIDER IMPLICATIONS: The themes of 'wrongful birth' and 'wrongful life' are charged with perplexing ethical dilemmas and raise delicate legal questions. These have met, in various countries and on certain occasions, with different solutions and have triggered ethical and juridical debate. The damage case scenarios result from a lack of information or diagnosis prior to the birth, which deprives the mother of the chance to terminate the pregnancy.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016
Our aim was to investigate whether advanced maternal age (!40 years) still impairs the outcome of... more Our aim was to investigate whether advanced maternal age (!40 years) 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 !40 years compared to <40 years (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. 2016 Elsevier Ireland Ltd. All rights reserved.
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Papers by Filiberto M. Severi