Folic acid fortification of flour to prevent neural tube defects in Europe - A position statement by the European Board and college of obstetrics and gynaecology (EBCOG).

Neural tube defects are disabling birth defects developing during the very early stages of conception. Children born with spina bifida face significant physical, psychological and social consequences. They may have bowel and urinary dysfunction, and no lower limb muscle control, resulting in lifelong wheelchair use. There is robust evidence that periconceptual folic acid supplementation prevents neural tube defects, when compared with no intervention. However, approximately 40% pregnancies in Europe are unplanned, and women may therefore not be taking prophylactic folic acid at the time of conception. There is evidence that low dose folic acid consumption via flour fortification provides further benefits in prevention of neural tube defects.

Fetal Deaths in Ireland Due to SARS-CoV-2 Placentitis Caused by SARS-CoV-2 Alpha.

CONTEXT.­: A severe third wave of COVID-19 disease affected Ireland in the first 3 months of 2021. In this wave, 1 second-trimester miscarriage and 6 stillbirths were observed in the Irish population because of placental insufficiency as a result of SARS-CoV-2 placentitis. This observation was at odds with the country's previous experience with COVID-19 disease in pregnant mothers. OBJECTIVE.­: To describe the clinical and pathologic features of these pregnancy losses. DESIGN.­: Retrospective review of clinical and pathologic data of cases of second-trimester miscarriage, stillbirth, or neonatal death identified by perinatal pathologists as being due to SARS-CoV-2 placentitis during the third wave of COVID-19 in Ireland. RESULTS.­: Clinical and pathologic data were available for review in 6 pregnancies. Sequencing or genotyping of the virus identified SARS-CoV-2 alpha (B.1.1.7) in all cases. Three of the 6 cases had maternal thrombocytopenia, and fetal growth restriction was not prominent, suggesting a rapidly progressive placental disease. CONCLUSIONS.­: The identification of SARS-CoV-2 alpha in all these cases suggests that the emergence of the variant was associated with an increased risk of fetal death due to SARS-CoV-2 placentitis when compared with the original virus. Maternal thrombocytopenia may have potential as a clinical marker of placentitis, but other inflammatory markers need investigation. Three of the 6 women had been assessed for reduced fetal movements in hospital some days before the fetal deaths actually occurred; this could suggest that there may be a window for intervention in some cases.

Prevalence and concordance of oral HPV infections with cervical HPV infections in women referred to colposcopy with abnormal cytology.

BACKGROUND: Considering the shared aetiology of Human Papillomavirus infections in oropharyngeal and cervical cancers and the possible role for sexual transmission, several key aspects of the relationship between cervical and oral infections merit investigation, including prevalence of concomitant oral HPV infection and type-specific concordance with concurrent cervical infections. METHODS: A cross-section study was performed on women referred to colposcopy clinics with cytological abnormalities and a cervical HPV infection. An oral rinse sample was taken from the participants at their baseline visit for HPV testing, and a demographic and risk factor questionnaire was also administered. HPV DNA testing was carried out on the Cobas 4800 platform and extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay. HPV genotyping was also carried out on the concurrent cervical tissue samples on all women who had a positive oral HPV infection. RESULTS: The prevalence of oral HPV infections was 10.0% (95%CI:5.9-13.7) in the study population. HPV18 was the most frequent genotype (7.0%). Concordant oral and cervical HPV infections were detected in 28.6% of women. Age (p = 0.005) and level of education (p = 0.02) were significantly associated with a prevalent oral HPV infection. CONCLUSION: Concomitant oral HPV infections were present in 10.0% of women referred to colposcopy with a pre-existing cervical HPV infections and cytological abnormalities. Although mild type-specific concordance was observed between oral and cervical HPV infections, findings suggest that infections at these sites may not be independent of each other.

HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status.

OBJECTIVES: To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy. METHODS: Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios. RESULTS: 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001. CONCLUSIONS: Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

Major obstetric haemorrhage: Incidence, management and quality of care in Irish maternity units.

OBJECTIVE: To assess major obstetric haemorrhage incidence, management and quality of care in Irish maternity units. DESIGN: In collaboration with Irish maternity units the National Perinatal Epidemiology Centre (Leitao et al., 2020) carried out a national clinical audit and surveillance of major obstetric haemorrhage (MOH). METHODS: MOH was defined as blood loss of at least 2500 ml, transfusion of five or more units of blood or documented treatment for coagulopathy. Co-ordinators in maternity units completed detailed case assessment forms. The denominator data obtained from the individual units was restricted to live births and stillbirths of babies weighing at least 500 g. International Classification of Diseases diagnostic codes from hospital discharge records were used to identify cases of postpartum haemorrhage (PPH) and blood transfusion. RESULTS: During the time period, 2011-2018, there was a 54 % increase in MOH, a 60 % increase in PPH and a 54 % increase in blood transfusion. For 497 reported cases of MOH in 2011-2013, the median estimated blood loss was 3000 ml (range: 600-13,000 ml) and uterine atony was the most common cause. At least one uterotonic agent was used to arrest the bleeding in 94 % of the 477 MOH cases associated with a vaginal or caesarean delivery. A blood transfusion was received in 93 % of cases. Regarding quality of care, the vast majority of reported cases were described as receiving appropriate care and were well managed. CONCLUSION: Internationally, obstetric haemorrhage and especially PPH and its increasing trend remains a major challenge for service providers and clinical staff. A standardisation of definitions of PPH/severe PPH/MOH and agreed approaches to quantitation of blood loss would be valuable developments to allow better investigation and shared learning. Reducing the burden of this morbidity through improvements in care should be a real focus of maternity services.

Medium-term outcomes of idiopathic ventricular fibrillation survivors and family screening: a multicentre experience.

AIMS: Early repolarization (ER) has been linked to poorer outcomes in idiopathic ventricular fibrillation (IVF). The role of family screening in IVF is not clear. Our aim was to review predictors for poorer outcomes and evaluate the role of family screening in IVF. METHODS AND RESULTS: This was a retrospective multicentre cohort study including all patients diagnosed with IVF. Data were collected on baseline characteristics, ECG findings, and recurrence of ventricular arrhythmia (VA) during follow-up. Electrocardiogram findings were reviewed in first-degree relatives that were screened. A total of 66 patients were included with male predominance (42/66, 64%) and Caucasian ethnicity (47/66, 71%). Mean age at cardiac arrest was 38 years ± 11. Thirty-one patients had ER (47%) predominantly with J-point amplitude ≥2 mm and horizontal ST segments (18/31, 58%). Recurrent VA was seen in 13 patients (20%). Horizontal ST segments were associated with increased rates of VA recurrence (OR 11, 95% CI 2.7-43.7; P = 0.0007). Early repolarization was seen in 20% of the 72 first-degree relatives and was more common if the proband had persistent ER pattern (OR 10.7, 95% CI 2.2-51.5; P = 0.003). CONCLUSION: Ventricular arrhythmia recurrence was lower than previously reported. Early repolarization was common in this IVF cohort, and horizontal ST segments were suggestive predictor for poorer outcomes. Persistent ER in proband was associated with ER in first-degree relatives. With better understanding of its predictive value and the relationship to IVF, this information could potentially be used to guide family screening and identify new mutations using family members with persistent ER.

Current concepts of anatomy and electrophysiology of the sinus node.

The sinoatrial node, or sinus node, of humans is the principal pacemaker of the heart. Over the last century, studies have unraveled the complex molecular architecture of the sinus node and the expression of unique ion channels within its specialized myocytes. Aim of this review is to describe the embriology, the anatomy, the histology and the electrophisiology of the sinus node.

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results.

INTRODUCTION: We describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF). METHODS: 40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line. RESULTS: At 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique. CONCLUSION: Linear ablation in the left and right atria to mimic Cox's Maze is feasible and safe using this ablating system.

Maternal cerebrovascular accidents in pregnancy: incidence and outcomes.

Stroke occurring during pregnancy and the postnatal period is a rare but potentially catastrophic event. The aim of this study was to examine the incidence and outcomes of pregnancies complicated by maternal stroke in a single centre. This is a prospective study of over 35,000 consecutive pregnancies over a four-year period at the National Maternity Hospital in Dublin from 2004 to 2008; in addition we also retrospectively examined all cases of maternal mortality at our institution over a 50-year period from 1959 to 2009. We prospectively identified eight cases of strokes complicating pregnancy and the postnatal period giving an overall incidence of 22.34 per 100,000 pregnancies or 24.74 per 100,000 deliveries. There were no stroke-related mortalities during that time. Retrospective analysis of maternal mortality revealed 102 maternal deaths over a 50-year period, 19 (18.6%) of which were due to cerebrovascular accidents. In conclusion, strokes complicating pregnancy and the puerperium remain a rare event and though there appears to be evidence that the incidence is increasing, the associated maternal mortality appears to be falling.

Severe maternal morbidity for 2004-2005 in the three Dublin maternity hospitals.

OBJECTIVE: To assess the prevalence and causes of severe maternal morbidity in Dublin over a two year period from 2004 to 2005. STUDY DESIGN: A prospective cohort study from January 2004 to December 2005 was undertaken in the three large maternity hospitals in Dublin, which serve a population of 1.5 million people. All are tertiary referral centres for obstetrics and neonatology and have an annual combined delivery rate of circa 23,000 births. Cases of severe maternal morbidity were identified. A systems based classification was used. The primary cause of maternal morbidity and the number of events experienced per patient was recorded. RESULTS: We identified 158 women who fulfilled the definition for severe maternal morbidity, giving a rate of 3.2 per 1000 maternities. There were two maternal deaths during the time period giving mortality to morbidity ratio of 1:79. The commonest cause of severe morbidity was vascular dysfunction related to obstetric haemorrhage. Eclampsia comprised 15.4% of cases. Intensive care or coronary care admission occurred in 12% of cases. CONCLUSION: The prevalence of severe maternal morbidity in this population is 3.2/1000 maternities. Obstetric haemorrhage was the main cause of severe maternal morbidity.

Asymmetric dimethylarginine and reduced nitric oxide bioavailability in young Black African men.

Black Africans have a higher incidence of cardiovascular disease than white Europeans. We explored potential mechanisms of this excess risk by assessing endothelium function, inflammatory status (C-reactive protein), oxidative stress (isoprostane-F2alpha), and plasma asymmetrical dimethyl arginine (ADMA; an endogenous competitive inhibitor of NO synthase) in each ethnic group. Thirty healthy black Africans and 28 well-matched white European male subjects were studied (mean age+/-SE: 32.2+/-0.9 and 29.2+/-1.2 years, respectively; P=0.07). High-resolution ultrasound was used to assess vascular function in the brachial artery by measuring flow mediated dilatation ([percentage of change]; endothelium-dependent function) and glyceryltrinitrate dilatation ([percentage of change]; endothelium-independent function). Blood pressure, fasting lipids, glucose, and estimated glomerular filtration rate levels were similar in both groups. There was no difference in C-reactive protein (black Africans: 0.8+/-0.1 mg/L; white Europeans: 0.6+/-0.1 mg/L; P=0.22), isoprostane-F2alpha (black Africans: 42.9+/-1.5 pg/mL; white Europeans: 39.2+/-1.5 pg/mL; P=0.23), and leptin (black Africans: 64.1+/-10.2 ng/mL; white Europeans: 47.8+/-9.8 ng/mL; P=0.37) levels between the 2 ethnic groups. However, compared with white Europeans, plasma ADMA levels were significantly higher in black Africans (0.34+/-0.02 micromol/L and 0.25+/-0.03 micromol/L; P=0.03). There was no difference in the percentage of glyceryltrinitrate dilatation (P=0.7), but the percentage of flow-mediated dilatation was significantly lower in black Africans (black Africans: 5.2+/-0.3; white Europeans: 6.3+/-0.4; P=0.02). In a stepwise multiple regression model, ADMA level was the only independent determinant of flow-mediated dilatation (P=0.02). In turn, race was the only independent determinant of ADMA levels (P=0.03). Our findings indicate that circulating ADMA levels are significantly higher in healthy black African males than in white European males. This may contribute to the lower NO bioavailability and higher incidence of cardiovascular disease seen in black Africans.

Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men.

OBJECTIVES: The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). METHODS AND RESULTS: 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. CONCLUSIONS: Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.