First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) are known to be associated with the development of pregnancy-related complications like small for gestational age infants, intrauterine fetal demise, gestational diabetes and preeclampsia. The study aims to find possible long-term correlations with the development of metabolic and cardiovascular complications in the mothers and their progeny in later life. This is a retrospective cohort study conducted on consecutive unselected women screened for chromosomal anomalies in the first trimester of pregnancy between 2004 and 2010. PAPP-A values as well as clinical data collected at childbirth were considered. A maternal and neonatal follow-up was performed through a telephone interview with the mother during 2015. The body-mass-index and the presence of cardiovascular diseases, dyslipidaemia and diabetes mellitus were evaluated. The analysis included 988 patients. The median time of follow-up was 7 years (IQR 6\u20139). Lower first trimester maternal blood PAPP-A quartiles were associated with small stature of the offspring (z-score 1st-2nd quartile 0.37 IQR 120.42 and 1.17 vs 3rd-4th quartile 0.67 IQR 120.17 and 1.36, p < 0.05). Furthermore, low first trimester PAPP-A in pregnancy without other gestations following the index one, in Kaplan-Meier analysis was associated to a significant increase of hypoglycemic agents use at 7 and 10 years (respectively 1.12% CI.95 0\u20132.38% and 5.45% CI.95 0\u201310.82%) compared to the control group of high first trimester PAPP-A values (0% CI.95 0\u20130%) (p < 0.05). Low PAPP-A serum levels in the first trimester of pregnancy are associated with short stature in offspring and de-novo development of maternal diabetes mellitus in later life

Building a Prediction Model for Vacuum-Assisted Operative Vaginal Delivery Risk

Aim: The objective of this study was to evaluate the risk factors for operative vaginal delivery and to propose a new nomogram for predicting the risk. Methods: We retrospectively analyzed the data of 1,955 pregnancies that occurred in our clinic between the years 2007 and 2008. Included were singleton pregnancies with labor diagnosis after the 36th gestational week in which spontaneous or operative vaginal deliveries occurred. In this study, the operative delivery was carried out exclusively by vacuum extraction. Results: After univariate analysis and multivariate logistic regression stepwise model selection, maternal age, nulliparity, medically assisted procreation, gestational age at birth, male fetus, epidural analgesia and medical induction of labor were found to be the most predictive variables for operative vaginal delivery. Considering these factors we propose a new nomogram for an objectified determination of the risk of operative vaginal delivery. Conclusions: The new nomogram we propose could be an important tool for an objectified determination of the risk of operative vaginal delivery by vacuum extraction in individualized patient counseling

Anthropometric Features and Third-Fourth Degree Perineal Tears

The main objective of this study was to evaluate the association between maternal and fetal anthropometric characteristics and third- and fourth-degree perineal tears. This retrospective cohort study considered all consecutive pregnancies from 2011 to 2017 at a single Institution. The inclusion criteria were: singletons who delivered vaginally during the study period, the presence of information on maternal pre-pregnancy weight, maternal height, and weight of the newborn. The feto-maternal body-mass index (BMI) was calculated as neonatal weight in kg on maternal height in squared meters (kg/m(2)). In total, 5397 singleton-term pregnancies were included; the prevalence of third-fourth-degree perineal tears was 0.47%. The most predictive factors were: nulliparity, feto-maternal BMI, neonatal weight, gestational age at delivery, and neonatal head circumference. After adjustment in multivariate analysis, the only independent predictors were nulliparity and fetomaternal BMI. The AUC of the final multivariate model was 73.54% (95% CI 65.65-81.42). Furthermore, feto-maternal BMI and gestational age had a significant direct correlation. Nulliparity and feto-maternal BMI are the two best predictors for third and fourth-degree perineal tears in our setting. Confirming this association in future research and integrating it into a decision algorithm on delivery timing could reduce obstetric damage to the anal sphincter

Evolution of human IgH3 ' EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites

The enhancer complex regulatory region at the 3' of the immunoglobulin heavy cluster (IgH3'EC) is duplicated in apes along with four constant genes and the region is highly conserved throughout humans. Both human IgH3'ECs consist of three loci high sensitive (HS) to DNAse I with enhancer activity. It is thus possible that the presence of structural divergences between the two IgH3'ECs and of relative polymorphisms correspond to functional regulatory changes. To analyse the polymorphisms of these almost identical regions, it resulted mandatory to identify the presence of divergent sequences, in order to select distinctive primers for specific PCR genomic amplifications. To this aim, we first compared the two entire IgH3'ECs in silicio, utilising the updated GenBank (GB) contigs, then we analysed the two IgH3'ECs by cloning and sequencing amplicons from independent genomes. In silicio analysis showed that several inversions, deletions and short insertions had occurred after the duplication. We analysed in detail, by sequencing specific regions, the polymorphisms occurring in enhancer HS1,2-A (which lies in IgH3'EC-1, 3' to the C alpha-1 gene) and in enhancer HS1,2-B (which lies in IgH3'EC-2, 3' to C alpha-2). Polymorphisms are due to the repetition (occurring one to four times) of a 38-bp sequence present at the 3' of the core of enhancers HS1,2. The structure of both human HS1,2 enhancers has revealed not yet described polymorphic features due to the presence of variable spacer elements separating the 38-bp repetitions and to variable external elements bordering the repetition cluster. We found that one of the external elements gave rise to a divergent allele 3 in the two clusters. The frequency of the different alleles of the two loci varies in the Italian population and allele 3 of both loci are very rare. The analysis of the Callicebus moloch, Gorilla gorilla and Pan troglodytes HS1,2 enhancers showed the transformation from the ancestral structure with the 31- to the 17-by external element in hominids. The relevance of the polymorphisms in the HS1,2 enhancers is due to the variable number of binding sites for the transcription factors: NF-kappa B, CMYB, BSAP1/2, AP1/4, E47, MyoD and mu E5 and thus to the possible influence of these variations on switch, production of Ig and on maturation of B cells. (c) 2004 Elsevier B.V. All rights reserved

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies

The region 3 ' to C alpha 1 gene of human IG heavy chain displays a polymorphic duplicated sequence and encodes an RNA associated with polysomes

A highly spread polymorphism flanking the 3 C alpha 1 human IG heavy chain gene was identified. This polymorphism allowed the detection of an internal duplication within the 3' flanking region of both C alpha 1 and C alpha 2. This region has a regulatory function with four enhancer structures also present at the 3' end of the human C alpha 2 as well as in that of mouse and rat single C alpha genes. The 5682-bp sequence of clone lambda p18 described here starts 3' of C alpha 1 and presents three open reading frames; one of them contains part of the tandem repeats with the 20-bp consensus described previously that is expressed in a poly(A)(+) RNA and found in three dbEST clones of the human tonsillar cDNA library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this transcript is associated with polysomes. We also discuss the possibility of the presence of a new regulatory gene that does not encode an immunoglobulin and maps in the human IG heavy chain gene cluster. (C) 1998 Elsevier Science B.V. All rights reserved

Modification of conservative treatment of heterotopic cervical pregnancy by Foley catheter balloon fixation with cerclage sutures at the level of the external cervical os: a case report

<p>Abstract</p> <p>Introduction</p> <p>Conservative treatment of a heterotopic cervical pregnancy was performed with a modification of the fixation of a Foley catheter at the level of the external cervical os, followed by the ligature of the descending cervical branches of the uterine arteries and systemic methotrexate application.</p> <p>Case presentation</p> <p>A 34-year-old Caucasian woman was diagnosed with double gestation after 6 weeks of <it>in vitro </it>fertilization treatment. A gynecological examination and color Doppler ultrasound scan revealed intra-uterine and cervical gestational sacs both containing live fetuses. A Foley catheter balloon was inserted into the cervical canal, inflated and fixed by a cerclage suture at the level of the external cervical os, followed by ligation of the descending cervical branches of the uterine arteries. Systemic methotrexate was applied. Three days after removal of the Foley catheter, an evacuation of the intra-uterine gestational sac was performed. Hemorrhage from the implantation site was controlled immediately and a pregnancy termination was successfully performed. The procedure was uneventful and our patient was discharged with a preserved uterus.</p> <p>Conclusions</p> <p>Conservative treatment of cervical pregnancy using a Foley catheter balloon is more efficacious if the Foley catheter balloon is attached in the correct position with a cerclage suture at the level of the external os, followed by ligation of the descending cervical branches of the uterine arteries, thereby exerting maximal pressure on the bleeding vessels.</p

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease

Background: Coeliac disease ( CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed. Methods: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). Results: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio ( OR) showed that those with 2/2 and 2/4 ( OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD ( OR 0.52, P = 0.01). Conclusions: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis

Impact of episiotomy on pelvic floor disorders and their influence on women's wellness after the sixth month postpartum: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The role of episiotomy as a protective factor against pelvic floor disorders postpartum has been debated for many years, but its routine use has been hitherto discouraged in the literature. Comparisons between restrictive and routine use of episiotomy in existent literature, however, fail to include any consideration relating to quality of life. The aim of this study, therefore, is to state the role of episiotomy in preserving the perineum from damage, in order to prevent the influence of pelvic floor disorders on women's psycho-physical wellness after the sixth month postpartum.</p> <p>Methods</p> <p>A follow-up telephone interview was performed among 377 primiparous and secondiparous Caucasian women who had a child by spontaneous or operative vaginal delivery in 2006 using a self-created questionnaire and King's Health Questionnaire (KHQ).</p> <p>Results</p> <p>The mean age at delivery was 35.26 (±4.68) years and episiotomy was performed in 59.2% of women. Multivariate linear regression shows episiotomy associated to higher quality of life after the sixth month postpartum by correlating with inferior values of King's Health Questionnaire (p < 0.05).</p> <p>Conclusions</p> <p>Episiotomy appears to be a protective factor for women's wellness. Women who had episiotomy and who experienced perineal symptoms have a better psycho-physical health status in the 12.79 months (±3.3) follow-up.</p

Breech presentation at term and associated obstetric risks factors-a nationwide population based cohort study

Purpose The aim of this study was to estimate whether breech presentation at term was associated with known individual obstetric risk factors for adverse fetal outcome. Methods This was a retrospective, nationwide Finnish population-based cohort study. Obstetric risks in all breech and vertex singleton deliveries at term were compared between the years 2005 and 2014. A multivariable logistic regression model was used to determine significant risk factors. Results The breech presentation rate at term for singleton pregnancies was 2.4%. The stillbirth rate in term breech presentation was significantly higher compared to cephalic presentation (0.2 vs 0.1%). The odds ratios (95% CIs) for fetal growth restriction, oligohydramnios, gestational diabetes, a history of cesarean section and congenital fetal abnormalities were 1.19 CI (1.07-1.32), 1.42 CI (1.27-1.57), 1.06 CI (1.00-1.13), 2.13 (1.98-2.29) and 2.01 CI (1.92-2.11). Conclusions The study showed that breech presentation at term on its own was significantly associated with antenatal stillbirth and a number of individual obstetric risk factors for adverse perinatal outcomes. The risk factors included oligohydramnios, fetal growth restriction, gestational diabetes, history of caesarean section and congenital anomalies.Peer reviewe