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"Penketh, Richard"
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Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes
2018
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.
Journal Article
Symptoms of Prenatal Depression Associated with Shorter Telomeres in Female Placenta
by
Baird, Duncan M.
,
Garay, Samantha M.
,
John, Rosalind M.
in
Anxiety
,
Anxiety Disorders - complications
,
Anxiety Disorders - psychology
2021
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.
Journal Article
The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age (SGA) infant
2019
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.
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.
'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).
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.
Journal Article
Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression
by
Penketh, Richard
,
Battersby, Alysia
,
Dunnett, Stephen B
in
Animal diseases
,
Animal models
,
Animals
2009
Rats are desensitized to xenografts of human neural or embryonic stem cell–derived cells by exposure to the xenogeneic cells during the neonatal period. Brain grafts survive in immunocompetent rats without chronic immunosuppression, allowing long-term studies.
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.
Journal Article
Persistence of anxiety symptoms after elective caesarean delivery
by
Penketh, Richard
,
Janssen, Anna B.
,
Garay, Samantha M.
in
Anxiety
,
anxiety disorders
,
Cesarean section
2018
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.
To determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales.
Prevalence of depression and anxiety were determined in women at University Hospital Wales (2015-16;
= 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.
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.
Women undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention.
None.
Journal Article
The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age
by
Penketh, Richard
,
Garay, Samantha M.
,
Janssen, Anna B.
in
Analysis
,
Cesarean section
,
Fetal development
2019
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. 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. '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). 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.
Journal Article
The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age
by
Penketh, Richard
,
Garay, Samantha M.
,
Janssen, Anna B.
in
Analysis
,
Cesarean section
,
Fetal development
2019
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. 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. '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). 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.
Journal Article
The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age
by
Savory, Katrina A
,
Penketh, Richard
,
Janssen, Anna B
in
Analysis
,
Cesarean section
,
Fetal development
2019
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. 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. '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). 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.
Journal Article
Laparoscopic excision of deep rectovaginal endometriosis in BSGE endometriosis centres: a multicentre prospective cohort study
by
Farthing, Alan
,
Ofuasia, Emmanuel
,
Clark, James
in
Bias
,
bowel endometriosis
,
Cohort analysis
2018
ObjectiveTo estimate the effectiveness and safety of laparoscopic surgical excision of rectovaginal endometriosis.DesignA multicentre, prospective cohort study.Setting51 hospitals accredited as specialist endometriosis centres.Participants5162 women of reproductive age with rectovaginal endometriosis of which 4721 women had planned laparoscopic excision.InterventionsLaparoscopic surgical excision of rectovaginal endometriosis requiring dissection of the pararectal space.Main outcome measuresStandardised symptom questionnaires enquiring about chronic pelvic pain, bladder and bowel symptoms, analgesia use and quality of life (EuroQol) completed prior to surgery and at 6, 12 and 24 months postoperatively. Serious perioperative and postoperative complications including major haemorrhage, infection and visceral injury were recorded.ResultsAt 6 months postsurgery, there were significant reductions in premenstrual, menstrual and non-cyclical pelvic pain, deep dyspareunia, dyschezia, low back pain and bladder pain. In addition, there were significant reductions in voiding difficulty, bowel frequency, urgency, incomplete emptying, constipation and passing blood. These reductions were maintained at 2 years, with the exception of voiding difficulty. Global quality of life significantly improved from a median pretreatment score of 55/100 to 80/100 at 6 months. There was a significant improvement in quality of life in all measured domains and in quality-adjusted life years. These improvements were sustained at 2 years. All analgesia use was reduced and, in particular, opiate use fell from 28.1% prior to surgery to 16.1% at 6 months. The overall incidence of complications was 6.8% (321/4721). Gastrointestinal complications (enterotomy, anastomotic leak or fistula) occurred in 52 (1.1%) operations and of the urinary tract (ureteric/bladder injury or leak) in 49 (1.0%) procedures.ConclusionLaparoscopic surgical excision of rectovaginal endometriosis appears to be effective in treating pelvic pain and bowel symptoms and improving health-related quality of life and has a low rate of major complications when performed in specialist centres.
Journal Article