Delivery after a previous cesarean section reviewed.

At the start of the 20th century, cesarean section (CS) was uncommon in obstetrics. By the end of the century, CS rates had increased dramatically worldwide. Although the explanation for the increase is multifactorial, a major driver in the ongoing escalation is the increase in women who are delivered by repeat CS. This is due, in part, to the fact that there has been a sharp fall in vaginal birth after CS (VBAC) rates as fewer women are offered a trial of labor after CS (TOLAC), due principally to fears of a catastrophic intrapartum uterine rupture. This paper reviewed international VBAC policies and trends. A number of themes emerged. The risk of intrapartum rupture and its associated complications is low and may sometimes be overestimated. Individual maternity hospitals in both developed and developing countries are inadequately resourced to safely supervise a TOLAC. Efforts to mitigate the risks of TOLAC by careful patient selection and good clinical practices may be underutilized. Given the serious short-term and long-term consequences of rising CS rates for women and for maternity services generally, a review of TOLAC policies worldwide should be prioritized and consideration given to convening a Global Consensus Development Conference on Delivery after CS.

ADAPTE with modified Delphi supported developing a National Clinical Guideline: stratification of clinical risk in pregnancy.

OBJECTIVES: Adaptation has been proposed as an alternative to de novo development to take advantage of existing clinical guidelines (guidelines) and reduce duplication. We describe the process of incorporating a modified Delphi method to reach formal consensus and inform locally relevant clinical recommendations during the development, through the ADAPTE process, of the Irish National Clinical Guideline No. 23 Stratification of Clinical Risk in Pregnancy. METHODS: A systematic search of guideline repositories, websites, and bibliographic databases was conducted. Quality appraisal was undertaken using AGREE II. Risk factors indicating the need for additional care were identified and extracted from high-quality guidelines. A three-round modified Delphi panel comprising healthcare stakeholders, was convened to agree and tailor risk factors. RESULTS: Of seven relevant international guidelines identified, three were considered high quality and contained a combined 59 risk factors potentially suitable for adaptation. Following the three-round Delphi process, 49 risk factors were included in the final guideline. Excluded risk factors were generally considered to be too broad to be useful for the Irish context. CONCLUSION: We believe that a formal consensus technique included within the ADAPTE process increased the rigor and transparency of this process and ensured the inclusion of more locally relevant risk factors.

Comparison of ultrasound with biomarkers to identify large-for-gestational age in women screened for gestational diabetes mellitus.

OBJECTIVE: Large-for-gestational-age (LGA) is associated with both fetal and maternal complications. One of the few modifiable risk factors for LGA is Gestational Diabetes Mellitus (GDM); for this reason, fetal growth is usually monitored by ultrasound in the third trimester. This prospective study compared a panel of ten established biomarkers measured at the time of selective screening for GDM at 26-28 weeks gestation with the ultrasound prediction of LGA. METHOD: Women were recruited using convenience sampling and consented at the first antenatal visit. Women with maternal risk factors for GDM attended for the one-step 75 g oral glucose tolerance test. An additional blood sample was taken for biomarker measurement. GDM was diagnosed according to the 2013 World Health Organization (WHO) criteria. Fetal biometry, including the abdominal circumference (AC) and the fetal abdominal subcutaneous tissue (FAST) thickness, were measured at 37 weeks gestation. RESULTS: Of the 195 women included, 105 (53.8%) had GDM. Of the 195 babies, 36 (18.5%) were LGA. Whether the woman had GDM or not, fetal biometry was strongly predictive of LGA but none of the following biomarkers measured at 26-28 weeks gestation alone or in combination were predictive: c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin. CONCLUSIONS: In women diagnosed with GDM, surveillance of fetal growth to identify LGA by ultrasound should continue in the third trimester. None of the ten established maternal biomarkers measured at the time of the OGTT was as strongly predictive of LGA as ultrasound.

Maternal obesity and depression reported at the first antenatal visit.

BACKGROUND: Maternal obesity and depression are common and both have been associated with adverse pregnancy outcomes. AIMS: The aim of this observational study was to examine the relationship between maternal body mass index (BMI) category and self-reported depression at the first antenatal visit. METHODS: Women who delivered a baby weighing ≥ 500 g over nine years 2009-2017 were included. Self-reported sociodemographic and clinical details were computerised at the first antenatal visit by a trained midwife, and maternal BMI was calculated after standardised measurement of weight and height. RESULTS: Of 73,266 women, 12,304 (16.7%) had obesity, 1.6% (n = 1126) reported current depression and 7.5% (n = 3277) multiparas reported a history of postnatal depression. The prevalence of self-reported maternal depression was higher in women who had obesity, > 35 years old, were socially disadvantaged, smokers, had an unplanned pregnancy and used illicit drugs. After adjustment for confounding variables, obesity was associated with an increased odds ratio (aOR) for current depression in both nulliparas (aOR 1.7, 95% CI 1.3-2.3, p < 0.001) and multiparas (aOR 1.8, 95% CI 1.5-2.1, p < 0.001) and postnatal depression in multiparas (aOR 1.4, 95% CI 1.3-1.5, p < 0.001). The prevalence of current depression was higher in women with moderate/severe obesity than in women with mild obesity (both p < 0.001). CONCLUSIONS: We found that self-reported maternal depression in early pregnancy was independently associated with obesity. The prevalence of depression increased with the severity of obesity. Our findings highlight the need for implementation of strategies and provision of services for the prevention and treatment of both obesity and depression.

Low-Dose Metformin Treatment Reduces In Vitro Growth of the LL/2 Non-small Cell Lung Cancer Cell Line.

Lung cancer maintains a relatively small survival rate (~19%) over a 5-year period and up to 80-85% of all lung cancer diagnoses are Non-Small Cell Lung Cancer (NSCLC). To determine whether metformin reduces non-small cell lung cancer (NSCLC) LL/2 cell growth, cells were grown in vitro and treated with metformin for 48 h. qPCR was used to assess genes related to cell cycle regulation and pro-apoptotic markers, namely Cyclin D, CDK4, p27, p21, and HES1. Treatment with 10 mM metformin significantly reduced HES1 expression (p = 0.011). Furthermore, 10 mM metformin treatment significantly decreased REDD1 (p = 0.0082) and increased p-mTOR Ser2448 (p = 0.003) protein expression. Control cells showed significant reductions in phosphorylated p53 protein expression (p = 0.0367), whereas metformin treated cells exhibited reduced total p53 protein expression (p = 0.0078). There were no significant reductions in AMPK, PKB/AKT, or STAT3. In addition, NSCLC cells were treated for 48 h. with 10 mM metformin, 4 µM gamma-secretase inhibitor (GSI), or the combination of metformin (10 mM) and GSI (4 µM) to determine the contribution of respective signaling pathways. Metformin treatment significantly reduced total nucleus expression of the proliferation maker Ki-67 with an above 65% reduction in Ki-67 expression between control and metformin-treated cells (p = 0.0021). GSI (4 µM) treatment significantly reduced Ki-67 expression by ~20% over 48 h (p = 0.0028). Combination treatment (10 mM metformin and 4 µM GSI) significantly reduced Ki-67 expression by more than 50% over 48 h (p = 0.0245). As such, direct administration of metformin (10 mM for 48 h) proved to be an effective pharmaceutical agent in reducing the proliferation of cultured non-small cell cancer cells. These intriguing in vitro results, therefore, support the further study of metformin in appropriate in vivo models as an anti-oncogenic agent and/or an adjunctive therapy.

Low-Dose Metformin as a Monotherapy Does Not Reduce Non-Small-Cell Lung Cancer Tumor Burden in Mice.

Non-small-cell lung cancer (NSCLC) makes up 80-85% of lung cancer diagnoses. Lung cancer patients undergo surgical procedures, chemotherapy, and/or radiation. Chemotherapy and radiation can induce deleterious systemic side effects, particularly within skeletal muscle. To determine whether metformin reduces NSCLC tumor burden while maintaining skeletal muscle health, C57BL/6J mice were injected with Lewis lung cancer (LL/2), containing a bioluminescent reporter for in vivo tracking, into the left lung. Control and metformin (250 mg/kg) groups received treatments twice weekly. Skeletal muscle was analyzed for changes in genes and proteins related to inflammation, muscle mass, and metabolism. The LL/2 model effectively mimics lung cancer growth and tumor burden. The in vivo data indicate that metformin as administered was not associated with significant improvement in tumor burden in this immunocompetent NSCLC model. Additionally, metformin was not associated with significant changes in key tumor cell division and inflammation markers, or improved skeletal muscle health. Metformin treatment, while exhibiting anti-neoplastic characteristics in many cancers, appears not to be an appropriate monotherapy for NSCLC tumor growth in vivo. Future studies should pursue co-treatment modalities, with metformin as a potentially supportive drug rather than a monotherapy to mitigate cancer progression.

The prediction of morbidity related to vaginal delivery in nulliparous women - A secondary analysis from the genesis multicenter trial.

OBJECTIVE: In the prospective multicenter Genesis study, we developed a prediction model for Cesarean delivery (CD) in term nulliparous women. The objective of this secondary analysis was to determine whether the Genesis model has the potential to predict maternal and neonatal morbidity associated with vaginal delivery. STUDY DESIGN: The national prospective Genesis trial recruited 2,336 nulliparous women with a vertex presentation between 39 + 0- and 40 + 6-weeks' gestation from seven tertiary centers. The prediction model used five parameters to assess the risk of CD: maternal age, maternal height, body mass index, fetal head circumference and fetal abdominal circumference. Simple and multiple logistic regression analyses were used to develop the Genesis model. The risk score calculated using this model were correlated with maternal and neonatal morbidity in women who delivered vaginally: postpartum hemorrhage (PPH), obstetric anal sphincter injury (OASI), shoulder dystocia, one- and five-minute Apgar score ≤ 7, neonatal intensive care (NICU) admission, cephalohematoma, fetal laceration, nerve palsy and fractures. The morbidities associated with spontaneous vaginal delivery were compared with those associated with operative vaginal delivery (OVD). The likelihood ratios for composite morbidity and the morbidity associated with OVD based on the Genesis risk scores were also calculated. RESULTS: A total of 1,845 (79%) nulliparous women had a vaginal delivery. A trend of increasing intervention and morbidity was observed with increasing Genesis risk score, including OVD (p < 0.001), PPH (p < 0.008), NICU admission (p < 0.001), low Apgar score at one-minute (p < 0.001) and OASI (p = 0.009). The morbidity associated with OVD was significantly higher compared to spontaneous vaginal delivery, including NICU admission (p < 0.001), PPH (p = 0.022), birth injury (p < 0.001), shoulder dystocia (p = 0.002) and Apgar score of<7 at one-minute (p < 0.001). The positive likelihood ratios for composite outcomes (where the OVD was excluded) increases with increasing risk score from 1.005 at risk score of 5% to 2.507 for risk score of>50%. CONCLUSION: In women who ultimately achieved a vaginal birth, we have shown more maternal and neonatal morbidity in the setting of a Genesis nomogram-determined high-risk score for intrapartum CD. Therefore, the Genesis prediction tool also has the potential to predict a more morbid vaginal delivery.

The advanced treatment of hydrogen bonding in quantum crystallography.

Although hydrogen bonding is one of the most important motifs in chemistry and biology, H-atom parameters are especially problematic to refine against X-ray diffraction data. New developments in quantum crystallography offer a remedy. This article reports how hydrogen bonds are treated in three different quantum-crystallographic methods: Hirshfeld atom refinement (HAR), HAR coupled to extremely localized molecular orbitals and X-ray wavefunction refinement. Three different compound classes that form strong intra- or intermolecular hydrogen bonds are used as test cases: hydrogen maleates, the tripeptide l-alanyl-glycyl-l-alanine co-crystallized with water, and xylitol. The differences in the quantum-mechanical electron densities underlying all the used methods are analysed, as well as how these differences impact on the refinement results.

CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals.

CrystalExplorer is a native cross-platform program supported on Windows, MacOS and Linux with the primary function of visualization and investigation of molecular crystal structures, especially through the decorated Hirshfeld surface and its corresponding two-dimensional fingerprint, and through the visualization of void spaces in the crystal via isosurfaces of the promolecule electron density. Over the past decade, significant changes and enhancements have been incorporated into the program, such as the capacity to accurately and quickly calculate and visualize quantitative intermolecular interactions and, perhaps most importantly, the ability to interface with the Gaussian and NWChem programs to calculate quantum-mechanical properties of molecules. The current version, CrystalExplorer21, incorporates these and other changes, and the software can be downloaded and used free of charge for academic research.

Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.

The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low-molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. However, this difference has non-negligible consequences for derived properties.

Trends in private maternity care in Ireland's capital during and after the Great Economic Recession 2009-2017.

BACKGROUND: Maternity care in hospitals in the Republic of Ireland is funded by a hybrid of public finance and private health insurance. AIMS: The aim of this longitudinal observational study was to investigate the annual trends in maternity care from 2009 to 2017 during and after the Great Economic Recession. METHODS: All women who delivered a singleton baby weighing ≥ 500 g during the 9 years (2009-2017) were included. Detailed clinical and sociodemographic details were computerised at the first antenatal visit by a trained midwife. Women who delivered their first baby during the study were analysed longitudinally if they delivered again during the 9 years. RESULTS: The mean age of the 73,266 women was 31.3 ± 5.6 years, 40.1% were nulliparas, and 70.3% were Irish-born. Overall, 75.2% opted for the public, 10.8% for the semi-private, and 14.0% for the private package of maternity care. Over the 9 years, the number of women choosing private and semi-private care decreased by 21.6% and 35.3%, respectively, whereas the number of women using public care increased by 12.3%. Most women opted for the same package of care in subsequent pregnancies. CONCLUSIONS: Ireland's recent economic recession was accompanied by an overall decrease in the number of women choosing private maternity care after 2009. Furthermore, economic recovery with increasing female employment after 2012 was not associated with a recovery in demand for private care. These findings have important implications for healthcare policies and for the future organisation and funding of our maternity services.

Caesarean section rates in women in the Republic of Ireland who chose to attend their obstetrician privately: a retrospective observational study.

BACKGROUND: Caesarean section (CS) rates are increasing and there are wide variations in rates internationally and nationally. There is evidence that women who attend their obstetrician privately have a higher incidence of CS than those who attend publicly. The purpose of this observational study was to further investigate why CS rates may be higher in women who chose to attend their obstetrician privately. METHODS: This study analysed data collected as part of the clinical records by midwives at the woman's first antenatal appointment in a large European maternity hospital. All women who delivered between the years 2009 and 2017 were included. Data were analysed both cross-sectionally and longitudinally. RESULTS: Overall, 73,266 women had a singleton pregnancy and 1830 had a multiple pregnancy. Of the packages of maternity care, 75.2% chose public, 10.8% chose semiprivate and 14.0% chose private. During the study, 11,991 women attended the hospital for their first and second pregnancies. Overall, women who attended privately were older and had higher proportions of infertility treatment and history of miscarriage (all p < 0.001) compared to those publicly-funded. Private patients were more likely to have a history of infertility, a history of miscarriage, a multiple pregnancy and to be ≥35 yrs. They had lower rates of obesity, smoking and illicit drug use in pregnancy (all p < 0.001). In women who chose private care, the overall rate of CS was higher compared to women choosing publicly-funded (42.7% vs 25.3%, p < 0.001) The increase was due to an increase in elective rather than emergency CS. The increase in elective CS fell after adjustment for clinical risks. In the longitudinal analysis, 89.7% chose the same package second time around. Women who changed from public to private care for the second pregnancy were more likely to have had a previous emergency CS or admission to the Neonatal Unit. CONCLUSIONS: This study suggests that the increased CS rate in women privately insured may be attributed, in part, to the fact that women who can afford health insurance choose continuity of care from a senior obstetrician because they are risk adverse and wish to have the option of an elective CS.

The impact of revised diagnostic criteria on hospital trends in gestational diabetes mellitus rates in a high income country.

OBJECTIVE: In 2010, national guidelines were published in Ireland recommending more sensitive criteria for the diagnosis of Gestational Diabetes Mellitus (GDM). The criteria were based on the 2008 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study and were endorsed subsequently by the World Health Organization (WHO). Screening nationally is selective based on risk factors. We examined the impact of the new criteria on hospital trends nationally for GDM over the 10 years 2008-17. RESEARCH DESIGN AND METHODS: Data from three national databases, the Hospital Inpatient Enquiry System (HIPE), National Perinatal Reporting System (NPRS) and the Irish Maternity Indicator System (IMIS), were analyzed using descriptive statistics, analysis of variance, and Poisson loglinear modelling. RESULTS: The overall incidence of GDM nationally increased almost five-fold from 3.1% in 2008 to 14.8% in 2017 (p ≤ 0.001). The incidence varied widely across maternity units. In 2008, the incidence varied from 0.4 to 5.9% and in 2017 it varied from 1.9 to 29.4%. There were increased obstetric interventions among women with GDM over the decade, specifically women with GDM having increased cesarean sections (CS) and induction of labor (IOL) (p ≤ 0.001). These trends were significant in large and mid-sized maternity hospitals (p ≤ 0.001). The increase in GDM diagnosis could not be explained by an increase in maternal age nationally over the decade. The data did not include information on other risk factors such as obesity. The increased incidence in GDM diagnosis was accompanied by a decrease in high birthweight ≥ 4.5 kg nationally. CONCLUSIONS: We found adoption of the new criteria for diagnosis of GDM resulted in a major increase in the incidence of GDM rates. Inter-hospital variations increased over the decade, which may be explained by variations in the implementation of the new national guidelines in different maternity units. It is likely to escalate further as compliance with national guidelines improves at all maternity hospitals, with implications for provision and configuration of maternity services. We observed trends that may indicate improvements for women and their offspring, but more research is required to understand patterns of guideline implementation across hospitals and to demonstrate how increased GDM diagnosis will improve clinical outcomes.

Gait and plantar sensation changes following massage and textured insole application in patients after anterior cruciate ligament reconstruction.

BACKGROUND: Gait impairments following anterior cruciate ligament reconstruction (ACLR) may contribute to reinjury or future osteoarthritis development. Recently, plantar cutaneous sensation deficits have been reported post-ACLR. These sensory deficits may influence gait and represent a mechanism through which to improve gait. RESEARCH QUESTION: Can established sensory interventions change sensation and gait in patients after ACLR and compared to healthy adults? METHODS: Twenty-two adults (n = 11 post-ACLR, age:20.5 ±â€¯1.9years, body mass index[BMI]:24.5 ±â€¯3.6 kg/m2; n = 11 healthy, age:20.7 ±â€¯1.4years, BMI:23.3 ±â€¯2.7 kg/m2) completed two sessions separated by 48 h. Gait and plantar cutaneous sensation were assessed pre- and post-intervention (massage or textured insoles). Gait analysis was completed using 3D motion capture at 1.4 m/s ±â€¯5% and standard inverse dynamics analysis. Plantar cutaneous sensation was assessed using Semmes Weinstein Monofilaments with a 4-2-1 stepping algorithm at the plantar aspect of the first metatarsal head, base of the fifth metatarsal, and lateral and medial malleoli. Plantar massage was a 5-minute massage to both feet. Textured insoles (coarse grit sandpaper) were worn while walking. Biomechanical data were assessed via mixed-models, repeated measures ANOVAs and 90 % confidence intervals. Wilcoxon Signed Rank tests and Mann-Whitney U tests evaluated plantar cutaneous sensation within and between groups, respectively. RESULTS: Knee adduction moment was lower in the ACLR versus the contralateral limb pre-massage. The vGRF was lower during the first half of stance but greater during the second half of stance in the ACLR versus the control group post-massage. Massage improved ACLR limb sensation over the first metatarsal head (P = 0.042) and medial malleolus (P = 0.027). Textured insole application improved ACLR limb sensation over the first (P = 0.043) and fifth (P = 0.027) metatarsals and medial malleolus (P = 0.028). SIGNIFICANCE: Plantar massage and textured insoles improved plantar cutaneous sensation in the ACLR limb. Neither intervention influenced gait. Improving plantar sensation may be beneficial for patients after ACLR; however, sensory interventions to improve gait are necessary.

Notch Inhibition via GSI Treatment Elevates Protein Synthesis in C2C12 Myotubes.

The role of Notch signaling is widely studied in skeletal muscle regeneration but little is known about its influences on muscle protein synthesis (MPS). The purpose of this study was to investigate whether Notch signaling is involved in the regulation of MPS. C2C12 cells were treated with a γ-secretase inhibitor (GSI), to determine the effect of reduced Notch signaling on MPS and anabolic signaling markers. GSI treatment increased myotube hypertrophy by increasing myonuclear accretion (nuclei/myotube: p = 0.01) and myonuclear domain (myotube area per fusing nuclei: p < 0.001) in differentiating C2C12 cells. GSI treatment also elevated myotube hypertrophy in differentiated C2C12s (area/myotube; p = 0.01). In concert, GSI treatment augmented pmTOR Ser2448 (p = 0.01) and protein synthesis (using SUnSET method) in myotubes (p < 0.001). Examining protein expression upstream of mTOR revealed reductions in PTEN (p = 0.04), with subsequent elevations in pAKT Thr308 (p < 0.001) and pAKT Ser473 (p = 0.05). These findings reveal that GSI treatment elevates myotube hypertrophy through both augmentation of fusion and MPS. This study sheds light on the potential multifaceted roles of Notch within skeletal muscle. Furthermore, we have demonstrated that Notch may modulate the PTEN/AKT/mTOR pathway.

Inter-hospital comparison of Cesarean delivery rates should not be considered to reflect quality of care without consideration of patient heterogeneity: An observational study.

OBJECTIVE: Contemporary approaches to monitoring quality of care in obstetrics often focus on comparing Cesarean Delivery rates. Varied rates can complicate interpretation of quality of care. We previously developed a risk prediction tool for nulliparous women who may require intrapartum Cesarean delivery which identified five key predictors. Our objective with this study was to ascertain if patient heterogeneity can account for much of the observed variation in Cesarean delivery rates, thereby enabling Cesarean delivery rates to be a better marker of quality of care. MATERIALS AND METHODS: This is a secondary analysis of the Genesis study. This was a large prospective study of 2336 nulliparous singleton pregnancies recruited at seven hospitals. A heterogeneity score was calculated for each hospital. An adjusted Cesarean delivery rate was also calculated incorporating the heterogeneous risk score. RESULTS: A cut-off at the 90th percentile was determined for each predictive factor. Above the 90th percentile was considered to represent 'high risk' (with the exception of maternal height which identified those below the 10th percentile). The patient heterogeneous risk score was defined as the number of risk factors > 90th percentile (<10th percentile for height). An unequal distribution of high-risk patients between centers was observed (p < 0.001). The correlation between the Cesarean delivery rate and the patient heterogeneous risk score was high (0.76, p < 0.05). When adjusted for patient heterogeneity, Cesarean delivery rates became closer aligned. CONCLUSION: Inter-institutional diversity is common. We suggest that crude comparison of Cesarean delivery rates between different hospitals as a marker of care quality is inappropriate. Allowing for marked differences in patient characteristics is essential for correct interpretation of such comparisons.

Maternal employment and pregnancy outcomes in a large European maternity hospital.

OBJECTIVE: Epidemiological studies have previously reported that maternal socioeconomic disadvantage is associated with adverse feto-maternal outcomes. However, little attention has been paid to the question of the woman's employment status. The aim of this observational study was to examine the relationship between maternal employment status at the first antenatal visit and pregnancy outcomes. STUDY DESIGN: The study was confined to women with a singleton pregnancy who attended for maternity care between the years 2010 and 2017 and delivered a baby weighing ≥500 g. Self-reported sociodemographic and clinical details were recorded at the first antenatal visit by a trained midwife and updated before hospital discharge. The hospital is one of the largest in Europe and accepts women from all socioeconomic groups, including women in the public system and those with private health insurance, across the rural-urban spectrum. RESULTS: Of the 62,395 women, the mean age was 31.5 years (SD 5.4), 39.3% were nulliparas and 70.7% were Irish born. Compared with the 45,028 (72.2%) women who reported as being in paid employment, the 4984 (8.0%) women who were unemployed had a higher rate of stillbirth (8/4984 vs. 27/45,028, p = 0.005) and homemakers had a higher incidence of neonatal death (31/12,383 vs. 73/45,028, p = 0.02). On multivariable analysis, women who were unemployed or homemakers had increased adjusted odds ratios for neonatal unit (NNU) admissions, preterm birth, low birth weight, and small-for-gestational-age. Compared to women in paid employment, women who were unemployed or homemakers were associated with younger age (<30 years) in pregnancy, multiparity, unplanned pregnancy, no or postconceptional only folic acid supplementation, anxiolytic/antidepressant use, as well as persistent smoking and illicit drug use during pregnancy. CONCLUSIONS: In a high-income European country, women who reported as unemployed or homemakers were associated with higher rates of adverse pregnancy outcomes. Furthermore, these women were associated with suboptimal lifestyle behaviours such as smoking and illicit drug use in early pregnancy. This highlights the need for long term public policies on female unemployment and retaining women with children in employment.

The use of biomarkers at the end of the second trimester to predict Gestational Diabetes Mellitus.

OBJECTIVE: Previous studies that investigated the relationship between biomarkers and gestational diabetes mellitus (GDM) generally focused on individual biomarkers with significant heterogeneity in terms of the screening methodologies, diagnostic criteria for GDM and sample handling of glucose within these studies. This prospective study used an established panel of ten biomarkers to determine if they could predict the diagnosis of GDM. STUDY DESIGN: Women with risk factors for GDM were recruited at their first antenatal visit. They attended for an oral glucose tolerance test at 26-28 weeks' gestation with strict preanalytical handling of glucose samples to minimise glycolysis. A fasting plasma sample taken simultaneously was stored at -80 °C and analysed in bulk for 10 biomarkers (insulin, c-peptide, glucagon, ghrelin, gastric inhibitory polypeptide (GIP), glucagon like peptide-1 (GLP-1), leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1)) using the Bio-plex-pro Human Diabetes Assay. RESULTS: Insulin and C-peptide levels in the third tertile were associated with the development of GDM (adjusted odds ratio (aOR) 2.6, 95 % CI 1.3-5.0, p = 0.005 and aOR 3.7, 95 % CI 1.8-7.4, p < 0.001 respectively, adjusted for maternal obesity). Elevated levels of ghrelin were associated with a lower odds of developing GDM, after adjustment for maternal obesity. However, approximately half of the women with GDM who were in the obesity category did not have insulin or c-peptide levels in the third tertile. CONCLUSIONS: While three of the ten biomarkers were statistically associated with an increased risk of GDM, the large overlap in values between those with normal and abnormal glucose tolerance meant that the biomarkers (alone or in combination) were not useful clinically.

Childbirth in Ireland's capital city over sixty years.

BACKGROUND: Ireland has changed over the past sixty years, and the dynamic practice of obstetrics and gynaecology has changed with it. STUDY DESIGN AND METHODS: To describe these changes, a review was performed of clinical reports of a tertiary referral teaching hospital over six decades. RESULTS: Since the 1960s, the hospital's total births per annum has risen (3050 to 8362 births). Teenage pregnancy is less common (4.7 to 2.0%, p < 0.001), with more women over age 40 at booking (2.6 to 6.4%, p < 0.001). There are more multiple pregnancies now (1.8 to 4.1%, p < 0.001) and less grand-multiparous woman (10.1 to 1.3%, p < 0.001). Eclampsia is less common (0.18 to 0.02%, p = 0.003), with a slight decrease in rate of preeclampsia (3.8 to 3.0%, p = 0.03). Induction of labour increased considerably (8.8 to 32.1%, p < 0.001). While the instrumental delivery rate remained stable, the instrument of choice has changed from forceps (11.3 to 5.4%, p = 0.001) to ventouse delivery (0.6 to 9.1%, p = 0.001). The caesarean section rate rose (5.9 to 29.7%, p < 0.001). Vaginal birth after caesarean section rate dropped (90.4 to 28.2%, p < 0.001) without significant change in rate of uterine rupture (0.4 to 0.7%, p = 0.1). The perinatal mortality rate improved (48.5 to 5.4 per 1000 births, p < 0.001). Preterm birth rate rose (4.9 to 6.6%, p = 0.001). Foetal macrosomia decreased in this time (2.5 to 1.7%, p = 0.007), despite a rise in the incidence of gestational diabetes mellitus. CONCLUSION: This study provides an intriguing glimpse into the changes in the practice of obstetrics and demonstrates how it adapts to the population it serves.