Symptoms of Prenatal Depression Associated with Shorter Telomeres in Female Placenta.

BACKGROUND: Depression is a common mood disorder during pregnancy impacting one in every seven women. Children exposed to prenatal depression are more likely to be born at a low birth weight and develop chronic diseases later in life. A proposed hypothesis for this relationship between early exposure to adversity and poor outcomes is accelerated aging. Telomere length has been used as a biomarker of cellular aging. We used high-resolution telomere length analysis to examine the relationship between placental telomere length distributions and maternal mood symptoms in pregnancy. METHODS: This study utilised samples from the longitudinal Grown in Wales (GiW) study. Women participating in this study were recruited at their presurgical appointment prior to a term elective caesarean section (ELCS). Women completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Telomere length distributions were generated using single telomere length analysis (STELA) in 109 term placenta (37-42 weeks). Multiple linear regression was performed to examine the relationship between maternally reported symptoms of depression and anxiety at term and mean placental telomere length. RESULTS: Prenatal depression symptoms were significantly negatively associated with XpYp telomere length in female placenta (B = -0.098, p = 0.026, 95% CI -0.184, -0.012). There was no association between maternal depression symptoms and telomere length in male placenta (B = 0.022, p = 0.586, 95% CI -0.059, 0.103). There was no association with anxiety symptoms and telomere length for either sex. CONCLUSION: Maternal prenatal depression is associated with sex-specific differences in term placental telomeres. Telomere shortening in female placenta may indicate accelerated placental aging.

Seasonal variation in salivary cortisol but not symptoms of depression and trait anxiety in pregnant women undergoing an elective caesarean section.

OBJECTIVES: Seasonal changes in mood and behaviour are commonly reported in the general population but considerably less is known regarding seasonality and pregnancy. This study investigated the relationship between seasons and depression and anxiety symptoms, salivary cortisol concentrations, custom birthweight centiles (CBWC) and placenta weight for pregnant women living in South Wales. METHODS: This study utilised data from the longitudinal Grown in Wales (GiW) cohort. Women were recruited at the presurgical elective caesarean section (ELCS) appointment, when they provided saliva samples and completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Data on birthweight and placental weight was extracted from medical notes. Seasonal data was available for 316 participants. RESULTS: No association was identified between seasons and EPDS (p = .178), STAI scores (p = .544), CBWC (p = .683) or placental weight (p = .857). Significance was identified between seasons and salivary cortisol concentration (p<.001), with highest levels in autumn and winter. Adjusted linear regression identified spring (B=-.05, p=.007, 95% CI -.09, -.01) and summer (B=-.06, p = .001, 95% CI -09, -.02) compared to autumn, and spring (B=-.05, p=.009, 95% CI -.09, -.01) and summer (B=-.06, p=.002, 95% CI -.10, -.02) compared to winter to be associated with decreased cortisol concentrations. CONCLUSION: This study found no association between season and maternally-reported mental health symptoms, birthweight by CBWC or placental weight but did between season and term salivary cortisol. This finding will have implications for studies that do not account for seasonality when using salivary cortisol as a biomarker.

The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age (SGA) infant.

OBJECTIVES: Maternal lifestyles, including diet, have been linked to infant birthweight. However, customised birthweight centiles (CBWC), which more accurately identify small babies that have increased fetal growth restriction and are at higher risk of newborn morbidity and later life health complications, are rarely considered when studying maternal diet. This study investigated maternal dietary patterns and their impact on infant CBWC within a cohort of women living in South Wales. METHODS: This study utilised cross-sectional data from the longitudinal Grown in Wales (GiW) cohort. Women 18-45 years old were recruited the morning prior to an elective caesarean section (ELCS). Women completed a food frequency questionnaire (FFQ). Additional data on pregnancy and birth outcomes was extracted from medical notes. Data from 303 participants was analysed. RESULTS: 'Western' and 'Health conscious dietary patterns were identified. The 'Health Conscious' dietary pattern was significantly associated with maternal BMI, age, education, income and exercise. Adjusted regression analyses indicated that greater adherence to a 'Health Conscious' dietary pattern was significantly associated with increased CBWC (AOR = 4.75 [95% CI: 1.17, 8.33] p = .010) and reduced risk of delivering a small-for-gestational age (SGA) infant (AOR = .51 [95% CI: .26, .99] p = .046). CONCLUSION: A healthier diet was significantly associated with higher birthweight using CBWC and a reduced risk of delivering an SGA infant suggesting that birthweight will be improved in areas of Wales by focused support encouraging healthier dietary habits.

Falling caesarean section rate and improving intra-partum outcomes: a prospective cohort study.

OBJECTIVE: To evaluate caesarean section (CS) rates and moderate to severe hypoxaemic ischaemic encephalopathy (HIE) rates with other core intra-partum outcomes following reconfiguration of maternity services in Cardiff, South Wales, UK. DESIGN: Cohort study of births from 2006 to 2015. SETTINGS: A University tertiary referral centre for foetal and maternal medicine with 6000 births/year, University Hospital of Wales, United Kingdom. METHOD: Data relating to births from 1 January 2006 to 31 December 2015 were extracted from the computerized maternity database on a yearly basis. Case notes of all mothers and babies for the same duration were hand searched for documentation of HIE. HIE data was also collected prospectively by neonatologist (SC) and obstetrician (PA). MAIN OUTCOME MEASURES: Incidence of caesarean section births, babies with moderate to severe HIE, instrumental vaginal births, obstetric anal sphincter injuries (OASIS) associated with instrumental delivery, and major post-partum haemorrhage (MPPH) of 2500 mL or more. RESULTS: During this 10-year period, a downward trend in emergency CS rate was seen from 15.6% in 2006 to 10.5% in 2015, reducing total CS rate from 25.5% in 2006 to 21.2% in 2015. A downward trend in the incidence of moderate and severe HIE was seen over the same period. There was an increase in operative vaginal births (OVB) from 12.8% to 15%. The rate of spontaneous vaginal births (SVB) remained stable. The incidence of OASIS remained constant and MPPH rate has fallen. CONCLUSIONS: Following amalgamation of two medium sized obstetric units and the opening of a Midwifery Led Unit (MLU), core intrapartum outcomes have improved. Contributing factors are the introduction of regular multidisciplinary training with enhanced team working, compulsory education for obstetricians and midwives on cardiotocograph (CTG) interpretation, increased consultant presence on delivery suite, robust risk management systems and broad multidisciplinary agreement on clinical guidelines promoting vaginal birth.

Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes.

Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher's least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children.

Persistence of anxiety symptoms after elective caesarean delivery.

BACKGROUND: In the UK, 11.8% of expectant mothers undergo an elective caesarean section (ELCS) representing 92 000 births per annum. It is not known to what extent this procedure has an impact on mental well-being in the longer term. AIMS: To determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales. METHOD: Prevalence of depression and anxiety were determined in women at University Hospital Wales (2015-16; n = 308) through completion of the Edinburgh Postnatal Depression Scale (EPDS; ≥13) and State-Trait Anxiety Inventory (STAI; ≥40) questionnaires 1 day prior to ELCS, and three postpartum time points for 1 year. Maternal characteristics were determined from questionnaires and, where possible, confirmed from National Health Service maternity records. RESULTS: Using these criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9-18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2-12.5) within 1 week, 8.7% (95% CI 4.2-13.8) at 10 weeks and 12.4% (95% CI 6.4-18.4) 1 year postpartum. Prevalence of reported anxiety symptoms was 27.3% (95% CI 22.5-32.4), 21.7% (95% CI 15.8-28.0), 25.3% (95% CI 18.5-32.7) and 35.1% (95% CI 26.3-44.2) at these same stages. Prenatal anxiety was not resolved after ELCS more than 1 year after delivery. CONCLUSIONS: Women undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention. DECLARATION OF INTEREST: None.

Feasibility of resectoscopic operative hysteroscopy in a UK outpatient clinic using local anesthetic and traditional reusable equipment, with patient experiences and comparative cost analysis.

STUDY OBJECTIVE: To assess procedural success, patient acceptability, and cost-saving potential of operative hysteroscopy using conventional equipment and local anesthetic in an outpatient clinic. DESIGN: Feasibility study/service evaluation (Canadian Task Force classification II-3). SETTING: Outpatient (office) clinic in a large UK teaching hospital. PATIENTS: One hundred eighteen women with diagnosed or suspected intrauterine myomas or polyps. INTERVENTIONS: Operative hysteroscopy (122 monopolar resection procedures using 8- or 10-mm diameter rigid resectoscopes with glycine solution for uterine irrigation) with the patient under local anesthesia in an outpatient (office) clinic. MEASUREMENTS AND MAIN RESULTS: Procedural success, duration of procedure, pathologic measurements, glycine irrigant deficit, patient pain scores and satisfaction, and comparative costs were recorded. Success of outpatient procedures was 90% (110 of 122 attempted), with a significantly reduced median procedure duration compared with a surgical setting using local (-7 minutes; p = .009) or general (-12.5 minutes; p < .001) anesthetic. Glycine irrigant absorption was low (median deficit, 0 mL), and no deficit was observed in 81% of patients. Mean (SD) estimated disease volume was comparable to that of hysteroscopic resection procedures in a surgical setting (3.38 [5.09] cm(3)), and weight was 1.8 (1.84) g. Patients tolerated the procedure well and reported low pain scores (highest median periprocedure pain measurement was 1.25 of 10), and 7-day follow-up satisfaction responses were positive. Retrospective cost analysis demonstrated that operative resection in an outpatient clinic was less expensive than in a surgical setting using general anesthetic (-$1003) or local anaesthetic (-$234). Reduced staff costs were the primary reason for this saving. CONCLUSIONS: Operative hysteroscopic resection of myomas and polyps is feasible and well tolerated by patients in an outpatient/office setting using local anaesthetic and conventional equipment. The outpatient procedure is less expensive and its duration is shorter than in a surgical setting.

Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression.

Preclinical development of human cells for potential therapeutic application in neurodegenerative diseases requires that their long-term survival, stability and functional efficacy be studied in animal models of human disease. Here we describe a strategy for long-term immune protection of human fetal and stem cell-derived neural cells transplanted into the adult rat brain, by desensitizing the host rat to similar cells in the neonatal period, without the need for additional immunosuppression.

Transrectal ultrasound and the diagnosis of rectovaginal endometriosis: a prospective observational study.

BACKGROUND: Rectovaginal endometriosis is a severe form of pelvic endometriosis in which pharmacological treatment is relatively ineffective (Vercellini et al., Fertil Steril. 2005;84:1375-87). Laparoscopic surgical treatment is effective, but has the potential risks of bowel perforation and colostomy formation (Darai et al., Am J Obstet Gynecol. 2005;192:394-400). Transrectal ultrasound scanning can be applied as a preoperative tool to predict the presence of rectovaginal endometriosis and bowel wall involvement (Abrao et al., J Am Assoc Gynecol Laparosc. 2004;11:50-4). METHODS: Thirty-two women underwent transrectal ultrasound followed by therapeutic laparoscopy. Likelihood ratios and post-test prevalences were calculated with Fagan's normogram. This was then extrapolated with the aid of a mathematical model to a low-risk population. RESULTS: A positive likelihood ratio was found to be 10.89 (95% confidence ratio (CI): 1.62-73.15) and a negative likelihood ratio was found to be 0.24 (95% CI: 0.1-0.57). The pre-test prevalence of rectovaginal endometriosis was 56%. The positive post-test prevalence probability was 93%, and the negative post-test prevalence probability was 23%. CONCLUSION: Preoperative transrectal ultrasound scanning for rectovaginal endometriosis is an extremely accurate predictive test, and strongly predicts the need for extensive laparoscopic dissection and potential bowel resection.

Gross vulval edema after laparoscopic instillation of 4% icodextrin solution.

Severe vulval edema after laparoscopic ovarian cystectomy with instillation of adhesion-prevention solution (4% icodextrin) is a rare complication. A 17-year-old girl was readmitted to the hospital 2 days after laparoscopic ovarian cystectomy with massive vulval swelling, pain, and anxiety. Gross swelling was potentially caused by accumulation of fluid 4% icodextrin in the labia. The condition resolved spontaneously with application of ice packs and bed rest. Possible mechanisms of this complication are discussed as is the importance of adequate counseling and consent before surgery when adhesion prevention solutions are to be administered.

Striatal graft projections are influenced by donor cell type and not the immunogenic background.

Reconstruction of CNS circuitry is a major aim of neural transplantation, and is currently being assessed clinically using foetal striatal tissue in Huntington's disease. Recent work suggests that neuronal precursors derived from foetal striatum may have a greater capacity than primary foetal striatum to project to the usual striatal target areas such as the globus pallidus and substantia nigra, raising the possibility that they have a greater potential for circuit reconstruction. However, comparing the reconstructive capacity of the two donor cells types is confounded by the fact that many precursor experiments have been carried out in a xenogeneic background in order to utilize species-specific markers for tracking the donor cells, whereas most primary foetal transplant studies have utilized an allograft paradigm. Thus, differences in immunogenic background could influence the findings; for example, xenogeneic grafts may not recognize host inhibitory signals, thereby encouraging more profuse and extensive projections. We have addressed this issue directly by comparing foetal neural precursor and primary foetal grafts in both allo- and xenograft environments using several labelling techniques, including GFP-transgenic mice and LacZ-labelled cells as donor tissue and iontophoretic injection of the anterograde tracers BDA, neurobiotin and PHA-L in the host. We present clear evidence that foetal neural precursors produce grafts with richer axonal outgrowth than primary foetal grafts, and that this is independent of the immunogenic background. Furthermore, both neural precursor and primary grafts derived from human foetal tissue produced a significantly richer outgrowth than do grafts of mouse donor tissue, which may relate to their large final graft volume and the greater intrinsic potential of human CNS neurons for greater axon elongation.