Khaled Ismail

Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders : the ISPMD Montreal consensus

Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion J Clin Psychiatry 5:30–39, 2003; Halbreich, Gynecol Endocrinol 19:320–334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive, universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD). The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health Organisation’s International Classification of Diseases (ICD-11), and the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field.

Accuracy of serum uric acid in predicting complications of pre‐eclampsia: a systematic review

Background  Pre‐eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre‐eclampsia.

Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans

Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.

The effectiveness of GnRHa with and without ‘add‐back’ therapy in treating premenstrual syndrome: a meta analysis

Objective  To determine the effectiveness of gonadotrophin‐releasing hormone analogues (GnRHa) with and without hormonal add‐back therapy in the management of premenstrual syndrome.

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

BackgroundProteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies.MethodsWe conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards.ResultsSixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission.ConclusionMeasure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia.

LINE-1 DNA methylation is inversely correlated with cord plasma homocysteine in man: A preliminary study

Folic acid supplementation during pregnancy has known beneficial effects. It reduces risk of neural tube defects and low birth weight. Folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. However, most data on the effects of folate on the epigenome is derived from animal or in vitro models. We examined the relationship between cord blood methylation and maternal folic acid intake, cord blood folate and homocysteine using data from 24 pregnant women. Genome-wide methylation was determined by the level of methylation of LINE-1 repeats using Pyrosequencing. We show that cord plasma homocysteine (p = 0.001, r = -0.688), but not serum folate or maternal folic acid intake, is inverse correlated with LINE-1 methylation. This remained significant after correction for potential confounders (p = 0.004). These data indicate that levels of folate-associated intermediates in cord blood during late pregnancy have significant consequences for the fetal epigenome.

Classification of episiotomy: towards a standardisation of terminology

Please cite this paper as: Kalis V, Laine K, de Leeuw J, Ismail K, Tincello D. Classification of episiotomy: towards a standardisation of terminology. BJOG 2012;119:522–526.

Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small‐for‐gestational age neonates: a population study, systematic review and meta‐analysis

To assess the effect of timing of folic acid (FA) supplementation during pregnancy on the risk of the neonate being small for gestational age (SGA).

How good are we at implementing evidence to support the management of birth related perineal trauma? A UK wide survey of midwifery practice

BackgroundThe accurate assessment and appropriate repair of birth related perineal trauma require high levels of skill and competency, with evidence based guideline recommendations available to inform UK midwifery practice. Implementation of guideline recommendations could reduce maternal morbidity associated with perineal trauma, which is commonly reported and persistent, with potential to deter women from a future vaginal birth. Despite evidence, limited attention is paid to this important aspect of midwifery practice. We wished to identify how midwives in the UK assessed and repaired perineal trauma and the extent to which practice reflected evidence based guidance. Findings would be used to inform the content of a large intervention study.MethodsA descriptive cross sectional study was completed. One thousand randomly selected midwives were accessed via the Royal College of Midwives (RCM) and sent a questionnaire. Study inclusion criteria included that the midwives were in clinical practice and undertook perineal assessment and management within their current role. Quantitative and qualitative data were collated. Associations between midwife characteristics and implementation of evidence based recommendations for perineal assessment and management were examined using chi-square tests of association.Results405 midwives (40.5%) returned a questionnaire, 338 (83.5%) of whom met inclusion criteria. The majority worked in a consultant led unit (235, 69.5%) and over a third had been qualified for 20 years or longer (129, 38.2%). Compliance with evidence was poor. Few (6%) midwives used evidence based suturing methods to repair all layers of perineal trauma and only 58 (17.3%) performed rectal examination as part of routine perineal trauma assessment. Over half (192, 58.0%) did not suture all second degree tears. Feeling confident to assess perineal trauma all of the time was only reported by 116 (34.3%) midwives, with even fewer (73, 21.6%) feeling confident to perform perineal repair all of the time. Two thirds of midwives (63.5%) felt confident to perform an episiotomy. Midwives qualified for 20 years or longer and those on more senior clinical grades were most likely to implement evidence based recommendations and feel confident about perineal management.ConclusionsThere are considerable gaps with implementation of evidence to support management of perineal trauma.

Manual perineal support at the time of childbirth: a systematic review and meta‐analysis

Genital tract trauma is common with vaginal births and is associated with significant morbidity, particularly with obstetric anal sphincter injuries (OASIS). Debate continues regarding the effectiveness of perineal support during childbirth in reducing the risk of trauma.