Placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a stepped wedge cluster randomised control trial (PARROT Ireland).

OBJECTIVE: To determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity. DESIGN: Stepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019. SETTING: National multisite trial in seven maternity hospitals throughout the island of Ireland PARTICIPANTS: Women with a singleton pregnancy between 20+0 to 36+6 weeks' gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate. INTERVENTION: Participants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment. MAIN OUTCOMES MEASURES: Co-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat. RESULTS: Of the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity-457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)-or in neonatal morbidity-527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67). CONCLUSIONS: This was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881073.

Association between preeclampsia and attention-deficit hyperactivity disorder: a population-based and sibling-matched cohort study.

OBJECTIVE: To examine the association between preeclampsia and attention-deficit hyperactivity disorder (ADHD), using a large Swedish-based registry cohort. METHODS: This study comprised 2 047 619 children, with 114 934 (5.6%) cases of ADHD. Preeclampsia was based on two alternate definitions: (i) preeclampsia (using ICD-9/ICD-10) and (ii) preeclampsia and small for gestational age (SGA) combined. ADHD was determined in one of two ways: (i) if a diagnosis of ADHD was present in the National Patient Register or (ii) if an individual was in receipt of ADHD medication in the Prescribed Drug Register. Multivariate Cox proportional hazards regression analysis allowed adjustment for several perinatal/sociodemographic factors. Sibling-matched analysis further controlled for shared genetic and familial confounding. RESULTS: In the adjusted Cox model, preeclampsia was associated with an increase in likelihood of ADHD (HR: 1.15, 95% CI: 1.12, 1.19). The HR for preeclampsia and those born SGA was 1.43 (95% CI: 1.31, 1.55) in the adjusted model, compared to those unexposed to preeclampsia/SGA. The sibling-matched analysis did not materially change these associations (HR: 1.13, 95% CI: 1.05, 1.22) and 1.55 (95% CI: 1.28, 1.88). CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA was associated with ADHD, independent of genetic/familial factors shared by siblings. However, it is important to note that sibling-matched analysis can only adjust for factors that are constant between pregnancies; therefore, residual confounding cannot be ruled out. Further research is needed to explore modifiable risk factors and identify those most-at-risk babies following delivery.

Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study.

The objective of this retrospective analysis of the longitudinal Millennium Cohort Study was to examine whether maternal alcohol consumption in pregnancy (MACP) is associated with the development of childhood autism spectrum disorders (ASD). Data on MACP and ASD were obtained from parental questionnaires. There were 18,168 singleton mother-child pairs with data on MACP, and 12,595 answered the question on ASD when the children were 11 years old. No statistically significant association was found between MACP and ASD for light (OR 0.78, 95% CI 0.48-1.29), moderate (OR 0.89, 95% CI 0.35-2.27), or heavy (OR 1.54, 95% CI 0.56-4.21) MACP. Alcohol consumption during pregnancy was not associated with the risk of developing ASD in this study cohort.

Critical review of reporting of the data analysis step in metabolomics.

INTRODUCTION: We present the first study to critically appraise the quality of reporting of the data analysis step in metabolomics studies since the publication of minimum reporting guidelines in 2007. OBJECTIVES: The aim of this study was to assess the standard of reporting of the data analysis step in metabolomics biomarker discovery studies and to investigate whether the level of detail supplied allows basic understanding of the steps employed and/or reuse of the protocol. For the purposes of this review we define the data analysis step to include the data pretreatment step and the actual data analysis step, which covers algorithm selection, univariate analysis and multivariate analysis. METHOD: We reviewed the literature to identify metabolomic studies of biomarker discovery that were published between January 2008 and December 2014. Studies were examined for completeness in reporting the various steps of the data pretreatment phase and data analysis phase and also for clarity of the workflow of these sections. RESULTS: We analysed 27 papers, published anytime in 2008 until the end of 2014 in the area or biomarker discovery in serum metabolomics. The results of this review showed that the data analysis step in metabolomics biomarker discovery studies is plagued by unclear and incomplete reporting. Major omissions and lack of logical flow render the data analysis' workflows in these studies impossible to follow and therefore replicate or even imitate. CONCLUSIONS: While we await the holy grail of computational reproducibility in data analysis to become standard, we propose that, at a minimum, the data analysis section of metabolomics studies should be readable and interpretable without omissions such that a data analysis workflow diagram could be extrapolated from the study and therefore the data analysis protocol could be reused by the reader. That inconsistent and patchy reporting obfuscates reproducibility is a given. However even basic understanding and reuses of protocols are hampered by the low level of detail supplied in the data analysis sections of the studies that we reviewed.

Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent.

AIM: To evaluate the reported use of data monitoring committees (DMCs), the frequency of interim analysis, prespecified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs). METHODS: We reviewed neonatal RCTs published in four high-impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11-year period (2003-2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria. RESULTS: Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association. A total of 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis, stopping rules were reported in 15 (21.4%) RCTs and seven (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed. CONCLUSION: While the majority of neonatal RCTs report on DMC involvement and interim analysis, there is still scope for improvement. Clear documentation of safety-related issues should be a central component of reporting in neonatal trials involving newborn infants.

Perinatal determinants of D-dimer levels in a cross-sectional study of low risk pregnant women.

BACKGROUND: To examine perinatal determinants of the antenatal levels of D-dimers. METHODS: Cross-sectional study of 760 low risk pregnant women recruited into five gestational groups. Variables examined in antenatal groups included maternal age, body mass index, parity, smoking, family history venous thromboembolism (VTE) and previous use of the oral contraceptive pill (OCP). Onset of labour and mode of delivery were also examined in the post-natal group. RESULTS: D-dimer levels in group 4 (38-40 + 6) were significantly lower in the women with a history of taking the OCP when compared to those that had not taken it in the past (P = 0.027). In the day 2 post-natal group, the median level of D-dimer was significantly higher in primparous when compared to multiparous women (P = 0.015). The median D-dimer levels were significantly lower in the elective Caesarean section group in comparison to spontaneous onset (P = 0.003) and induction of labour (P = 0.016). When the mode of delivery was examined, the median D-dimer levels were significantly lower in those that had an elective Caesarean section when compared to normal vaginal delivery (P = 0.008) and instrumental vaginal delivery (P = 0.007). Women post elective Caesarean section had a significantly lower D-dimer than those after emergency Caesarean section (P = 0.008). DISCUSSION: There are some significant differences in D-dimer levels when certain perinatal determinants are examined. This work is potentially beneficial to the future diagnosis of VTE in pregnancy as it supports previously published recommended D-dimer levels for the diagnosis of VTE in pregnancy.

Parental physical and lifestyle factors and their association with newborn body composition.

OBJECTIVE: To investigate the parental physical and lifestyle determinants of newborn body composition. DESIGN: Prospective cohort study. SETTING: Cork University Maternity Hospital, a tertiary referral hospital in Cork, Ireland. POPULATION: All babies were recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). These babies were recruited from women who had participated in the Screening of Pregnancy Endpoints (SCOPE) study Ireland, a prospective, multicentre cohort study METHODS: Multivariate linear regression was used to analyse the effect of a range of maternal and paternal physical and lifestyle features on neonatal body fat percentage (BF%). MAIN OUTCOME MEASURES: Neonatal BF%. Neonatal adiposity was assessed within 48 hours of birth using air displacement plethysmography (PEAPOD(®) ). RESULTS: In all, 1243 infants were enrolled in the study. Increasing maternal body mass index (adjusted mean difference 0.09; 0.04, 0.15) and waist height ratio (adjusted mean difference 6.59; 0.27, 12.92) were significantly associated with increased neonatal BF%. In contrast, maternal smoking was associated with reduced neonatal BF% compared with non smokers (adjusted mean difference -0.55; -1.07, -0.03). Infant sex significantly altered neonatal BF%, with female infants having higher neonatal BF% compared with male infants (adjusted mean difference 1.98; 1.54, 2.53). No association was observed between paternal body mass index (BMI), paternal age or paternal smoking and neonatal BF%. CONCLUSIONS: Maternal smoking, BMI, waist height ratio and infant sex were associated with altered BF%. TWEETABLE ABSTRACT: Maternal smoking, BMI, waist height ratio and infant sex are associated with altered neonatal body fat percentage.

Time to subsequent live birth according to mode of delivery in the first birth.

OBJECTIVE: To estimate the rate and time to next live birth by mode of delivery. DESIGN: Hospital-based cohort. SETTING: Aarhus University Hospital (AUH), Denmark. POPULATION: All pregnant women attending AUH were invited to enroll in the Aarhus Birth Cohort (ABC) study between 1989 and 2010 (n = 91,625). METHODS: Women were followed from their first live birth until the subsequent live birth or until censoring due to study end using Cox regression models. MAIN OUTCOME MEASURES: Rate and time to subsequent live birth according to mode of delivery. RESULTS: 46,162 index live births were identified, of which 22,462 (49%) had a subsequent live birth. Women with any type of caesarean had a 6% reduction in the rate of subsequent live birth (HR 0.94, 95% CI 0.89, 0.98), which remained unchanged in the analysis by type (emergency, HR 0.95, 95% CI 0.89, 1.02; elective, HR 0.91, 95% CI 0.85, 0.98) compared with women who had a spontaneous vaginal delivery (SVD). Operative vaginal delivery was associated with an 8% reduction in subsequent live birth rates (HR 0.92, 95% CI 0.86, 0.98) and vaginal delivery complicated by shoulder dystocia with a 19% reduction compared with SVD. Median time to next birth in days was shortest in women with a first caesarean (994 days, 95% CI 973, 1026) and longest in women with a vaginal delivery complicated by shoulder dystocia (1065 days, 95% CI 994, 1191). In women with planned pregnancies, the shortest median time to second birth was in women with breech vaginal deliveries (859 days, 95% CI 737, 1089) and the longest in women with vaginal deliveries complicated by shoulder dystocia (1193 days, 95% CI 1028, 1430). CONCLUSION: The impact of mode of delivery on subsequent rate and time to next birth was minimal in this study. The greatest reduction was among women with assisted vaginal delivery complicated by shoulder dystocia. This study is strengthened by data on pregnancy planning as well as information on complications of pregnancy, delivery and neonatal morbidities, all of which may influence a woman's decision on subsequent birth.

Previous pregnancy loss has an adverse impact on distress and behaviour in subsequent pregnancy.

OBJECTIVE: To investigate whether women with previous miscarriages or terminations have higher levels of anxiety, depression, stress, and altered behaviours in a subsequent pregnancy. DESIGN: A retrospective analysis of 5575 women recruited into the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study. SETTING: Auckland, New Zealand, Adelaide, Australia, Cork, Ireland, and Manchester, Leeds, and London, UK. POPULATION: Healthy nulliparous women with singleton pregnancies. METHODS: Outcomes were recorded at 15 and 20 weeks of gestation. MAIN OUTCOME MEASURES: Short-form State-Trait Anxiety Inventory (STAI) score, Perceived Stress Scale score, Edinburgh Postnatal Depression Scale score, and pregnancy-related behaviour measured using behavioural responses to pregnancy score. RESULTS: Of the 5465 women included in the final analysis, 559 (10%) had one and 94 (2%) had two previous miscarriages, and 415 (8%) had one and 66 (1%) had two previous terminations of pregnancy. Women with one previous miscarriage had increased anxiety (adjusted mean difference 1.85; 95% confidence interval, 95% CI 0.61-3.09), perceived stress (adjusted mean difference 0.76; 95% CI 0.48-1.03), depression (adjusted odds ratio, aOR 1.26; 95% CI 1.08-1.45), and limiting/resting behaviour in pregnancy (adjusted mean difference 0.80; 95% CI 0.62-0.97). In women with two miscarriages, depression was more common (aOR 1.65; 95% CI 1.01-2.70) and they had higher scores for limiting/resting behaviour in pregnancy (adjusted mean difference 1.70; 95% CI 0.90-2.53) at 15 weeks of gestation. Women with one previous termination displayed elevated perceived stress (adjusted mean difference 0.65; 95% CI 0.08-1.23) and depression (aOR 1.25; 95% 1.08-1.45) at 15 weeks of gestation. Women with two previous terminations displayed increased perceived stress (adjusted mean difference 1.43; 95% CI 0.00-2.87) and depression (aOR 1.67; 95% 1.28-2.18). CONCLUSIONS: This study highlights the psychological implications of miscarriage and termination of pregnancy.

Gestation-specific D-dimer reference ranges: a cross-sectional study.

OBJECTIVE: To establish a gestation-specific reference range for D-dimer in healthy pregnant women with a singleton pregnancy using the Auto-Dimer assay. DESIGN: Cross-sectional study SETTING: Cork University Maternity Hospital, Ireland. POPULATION: Healthy pregnant women attending for routine antenatal care. METHODS: Simultaneous-quantile regression was performed to construct a median, 5th percentile, and 95th percentile, model of normal pregnancy D-dimer concentration versus gestational week, ranging from week 6 to 42. Additionally, pair-wise Mann-Whitney U-tests were performed to compare distributions of D-dimer concentrations for each of the four discrete gestational sampling windows with the distribution of D-dimer concentrations 48 hours postpartum. MAIN OUTCOME MEASURES: D-dimer concentrations (ng/ml) during normal gestation (approximately week 6 to week 42). RESULTS: Seven hundred and sixty healthy pregnant women were investigated between gestational age week 5 and 48 hours postpartum. There was a clear steady increase in median D-dimer concentrations over the complete gestational period. Additionally, the 95th centile estimates for all gestational time-points were above the accepted non-pregnancy normal cut-off concentration (224 ng/ml). The results of the Mann-Whitney U-tests suggested that the long-term postnatal return to normal D-dimer concentrations begins in the immediate postpartum period. CONCLUSIONS: We found that there is a continuous increase in D-dimer concentrations across all gestations. This research is potentially beneficial to future diagnosis of venous thromboembolism (VTE) in pregnancy using the new recommended 95th centile potential cut-offs. Possible further investigation involves an observational study comparing D-dimer concentrations in women with proven DVT with those that don't, generating likelihood ratios.

Status of the pelvic floor in young primiparous women.

OBJECTIVES: To investigate the postnatal prevalence of sonographically diagnosed pelvic floor trauma, and the correlations with various antenatal/intrapartum predictors in primiparous women. METHODS: This was a prospective cohort study performed in a tertiary hospital with 9000 deliveries per annum. Of those invited, 202 (23.2%) primiparous participants were assessed clinically at least 1 year after delivery by Pelvic Organ Prolapse Quantification (POP-Q), two/three-dimensional transperineal sonography and quantification of serum collagen type III levels. RESULTS: There was a high prevalence of clinically significant pelvic organ prolapse (POP) on POP-Q staging: uterine prolapse, 63%; cystocele, 42%; and rectocele, 23%. Ballooning of the levator ani muscle (LAM) hiatus was detected in 33% and LAM avulsion in 29% of participants, with partial LAM avulsion occurring in 15% and complete avulsion in 14%. Postnatal POP symptoms (odds ratios (ORs) given here for presence of multiple prolapse symptoms) were positively associated with similar prepregnancy symptoms (OR, 7.2 (95% CI, 1.19-44.33)), LAM avulsion (OR, 4.8 (95% CI, 1.99-11.34)) and forceps delivery (borderline significance; OR, 1.8 (95% CI, 0.96-3.25)) and negatively associated with elective (OR, 0.2 (95% CI, 0.09-0.63)) and emergency (OR, 0.3 (95% CI, 0.12-0.83)) Cesarean section. LAM abnormality was associated with forceps delivery (OR, 4.9 (95% CI, 1.44-16.97)) and prolapse (OR, 6.8-11.7 (95% CI, 2.34-78.51)), whereas collagen levels did not play a role (OR, 1.001 (95% CI, 0.99-1.02)). CONCLUSIONS: Clinically significant POP was common in relatively young premenopausal primiparous women. Partial or full levator avulsion was seen in 29% of participants and was associated with POP and related symptoms. Congenital factors seem to play little role in the etiology of LAM trauma, and the main risk factor seems to be forceps delivery. Avoidance of difficult vaginal deliveries may prevent severe pelvic floor trauma.

Second-trimester maternal distress increases the risk of small for gestational age.

BACKGROUND: The effect of prenatal distress on the risk of a small for gestational age (SGA) infant is uncertain. We have addressed the influences of prenatal stress, anxiety and depression on the risk of SGA. We also examined the effects of infant sex and timing of distress during pregnancy on any observed associations. METHOD: The study population comprised 5606 healthy nulliparous pregnant women who participated in the international prospective Screening for Obstetric and Pregnancy Endpoints (SCOPE) study. Women completed the Perceived Stress Scale (PSS), the short form of the Spielberger State-Trait Anxiety Inventory (STAI) and the Edinburgh Postnatal Depression Scale (EPDS) at 15 ± 1 and 20 ± 1 weeks' gestation. SGA was defined as birthweight below the 10th customized percentile. Logistic regression was used for data analysis, adjusting for several potential confounders such as maternal age, body mass index (BMI), smoking, socio-economic status and physical exercise. RESULTS: The risk of SGA was increased in relation to mild [adjusted odds ratio (aOR) 1.35, 95% confidence interval (CI) 1.07-1.71], moderate (aOR 1.26, 95% CI 1.06-1.49), high (aOR 1.45, 95% CI 1.08-1.95) and very high stress scores (aOR 1.56, 95% CI 1.03-2.37); very high anxiety score (aOR 1.45, 95% CI 1.13-1.86); and very high depression score (aOR 1.14, 95% CI 1.05-1.24) at 20 ± 1 weeks' gestation. Sensitivity analyses showed that very high anxiety and very high depression increases the risk of SGA in males but not in females whereas stress increases the risk of SGA in both males and females. CONCLUSIONS: These findings suggest that prenatal stress, anxiety and depression measured at 20 weeks' gestation increase the risk of SGA. The effects of maternal anxiety and depression on SGA were strongest in male infants.

The role of prepregnancy pelvic floor dysfunction in postnatal pelvic morbidity in primiparous women.

INTRODUCTION AND HYPOTHESIS: Little is known about the natural history of pelvic floor dysfunction (PFD). We investigated the association between prepregnancy and postnatal PFD in premenopausal primiparous women and the associated effect of mode of delivery. METHODS: A prospective cohort study, nested within the parent Screening for Pregnancy Endpoints (SCOPE) study, was performed in a tertiary referral teaching hospital with approximately 9,000 deliveries per annum. The validated Australian pelvic floor questionnaire was completed by 872 nulliparous women at 15 weeks' gestation, at the time of recruitment to the SCOPE study and 1 year postnatally. The questionnaire contained four sections with questions about urinary, faecal, prolapse and sexual dysfunction. RESULTS: One year postnatally urinary dysfunction was present in 73%, faecal in 49%, prolapse in 14% and sexual in 58% of participants. Prepregnancy PFD persistent postnatally constituted more than half of total PFD. The majority of affected (71%) had multicompartment involvement. Participants with persistent PFD had higher prevalence of severe symptoms and bothersome symptoms within the group. Severity of prepregnancy PFD worsened in <15% cases postnatally. CONCLUSIONS: The main damage to the pelvic floor seems to occur in the majority of patients before first pregnancy, where first childbearing does not worsen prepregnancy PFD in the majority of cases. Pregnancy appears to affect more pre-existing symptoms of urgency and urge incontinence comparing to stress incontinence. Caesarean section seems to be more protective against postnatal worsening of prepregnancy PFD comparing to de novo onset pathology. However, larger studies are needed to confirm these findings.

Prevalence, etiology and risk factors of pelvic organ prolapse in premenopausal primiparous women.

INTRODUCTION: The natural history of pelvic organ prolapse (POP) is poorly understood. We investigated the prevalence and risk factors of postnatal POP in premenopausal primiparous women and the associated effect of mode of delivery. METHODS: We conducted a prospective cohort study in a tertiary teaching hospital attending 9,000 deliveries annually. Collagen-diseases history and clinical assessment was performed in 202 primiparae at ≥ 1 year postnatally. Assessment included Pelvic Organ Prolapse Quantification (POP-Q) system, Beighton mobility score, 2/3D-transperineal ultrasound (US) and quantification of collagen type III levels. Association with POP was assessed using various statistical tests, including logistic regression, where results with p < 0.1 in univariate analysis were included in multivariate analysis. RESULTS: POP had a high prevalence: uterine prolapse 89 %, cystocele 90 %, rectocele 70 % and up to 65 % having grade two on POP-Q staging. The majority had multicompartment involvement, and 80 % were asymptomatic. POP was significantly associated with joint hypermobility, vertebral hernia, varicose veins, asthma and high collagen type III levels (p < 0.05). In multivariate logistic regression, only levator ani muscle (LAM) avulsion was significant in selected cases (p < 0.05). Caesarean section (CS) was significantly protective against cystocele and rectocele but not for uterine prolapse. CONCLUSIONS: Mild to moderate POP has a very high prevalence in premenopausal primiparous women. There is a significant association between POP, collagen levels, history of collagen disease and childbirth-related pelvic floor trauma. These findings support a congenital contribution to POP etiology, especially for uterine prolapse; however, pelvic trauma seems to play paramount role. CS is significantly protective against some types of prolapse only.

Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

BACKGROUND: Preconception, prenatal and postnatal maternal stress is associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt and completed suicide. METHOD: Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992-2000 for childhood outcomes and 2,155,221 offspring born 1973-1997 for adult outcomes with follow-up to 2009. Maternal stress was defined as death of a first-degree relative during (a) the 6 months before conception, (b) pregnancy or (c) the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HRs) in unadjusted and adjusted analyses. RESULTS: Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third-trimester prenatal stress increased the risk of ASD [adjusted HR (aHR) 1.58, 95% confidence interval (CI) 1.15-2.17] and ADHD (aHR 1.31, 95% CI 1.04-1.66). First postnatal year stress increased the risk of offspring suicide attempt (aHR 1.13, 95% CI 1.02-1.25) and completed suicide (aHR 1.51, 95% CI 1.08-2.11). Bereavement stress during the second postnatal year increased the risk of ASD (aHR 1.30, 95% CI 1.09-1.55). CONCLUSIONS: Further research is needed regarding associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases the risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases the risk of offspring suicide attempt, completed suicide and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.

Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management.

AIM: To evaluate the performance of breast magnetic resonance imaging (MRI) in determining the size of invasive lobular carcinoma (ILC) compared to histopathology, and its influence on breast surgical management. MATERIALS AND METHODS: Prospective evaluation was undertaken of standardized contrast-enhanced MRI images of 51 consecutive women over an 18 month period with pure ILC or with lobular features as the dominant subtype on breast core biopsy. Image interpretation was performed by one consultant radiologist (M.H.). The lesion size at MRI was compared with the size at final histopathology after surgical excision using a Bland-Altman agreement plot. RESULTS: Of the 51 prospectively imaged consecutive women, seven were excluded as they had diffuse ILC. The remaining 44 patients had a mean histological tumour size of 34.9 mm (range 4-77 mm). MRI underestimated tumour size in 26 (59.1%) cases. In 21 (47.7%) patients, this discrepancy was small, ranging up to 16 mm. The largest underestimation occurred in five (11.4%) cases with a difference ranging between 31 and 48 mm. Fifteen (34.1%) tumours were overestimated by MRI where the discrepancy ranged up to 22 mm. In three (6.8%) patients MRI and histological size matched. The Bland-Altman agreement plot demonstrated that in 95% of cases the size at histopathology will be between 0.36 and 2.31 times the MRI size at extremes. MRI correlated better with histopathology in tumours up to T2 (<5 cm) size leading to a change in surgical management for nine of the 44 (20.5%) patients. CONCLUSION: MRI enables surgical management decisions to be made with increased confidence in patients with ILC up to T2 size.

An insight into pelvic floor status in nulliparous women.

INTRODUCTION AND HYPOTHESIS: Few studies have comprehensively investigated the prevalence of various types of pelvic floor Dysfunction (PFD) in women before their first pregnancy. However, no previous studies have investigated in detail all four compartments of PFD and the correlation between them. METHODS: This was a cross-sectional study nested within a parent prospective study Screening for Pregnancy Endpoints (SCOPE) performed in a tertiary referral teaching hospital with approximately 9,000 deliveries per annum. Nulliparous women completed the validated Australian Pelvic Floor Questionnaire at 15 weeks' gestation, at the time of recruitment to the SCOPE study. The questionnaire contained four sections, with questions about urinary, faecal, prolapse and sexual dysfunction in the prepregnancy period. RESULTS: A total of 1,484 participants completed the prenatal questionnaire. Urinary dysfunction was present in 61 % of participants, faecal in 41 %, prolapse in 5 % and sexual in 41 %; in 37 %, dysfunction was perceived as bothersome . At least one clinically significant symptom, defined as severity grade 2 or 3, or grade 1 associated with being bothersome, was reported by 58.2 % of participants. More than one type of PFD was present in 57.6 % of cases. The severity score of each symptom within a PFD section was associated with total section score. CONCLUSIONS: We confirmed a high rate of PFD in nulliparous women. Clinically significant symptoms and associated bother were very common among symptomatic participants. The majority of affected women had more than one type of PFD. Postnatal follow-up is needed in order to elucidate the role of prepregnancy symptoms in the aetiology of postnatal pelvic floor pathology.

Caesarean section and subsequent ectopic pregnancy: a systematic review and meta-analysis.

BACKGROUND: Caesarean section rates are increasing worldwide, and the long-term effects are unknown. OBJECTIVE: To evaluate the risk of subsequent ectopic pregnancy in women with a previous caesarean section, compared with vaginal delivery. SEARCH STRATEGY: Systematic review of the literature using CINAHL, the Cochrane Library, Embase, Medline, PubMed, SCOPUS and Web of Knowledge, published from 1945 until 17 July 2011. SELECTION CRITERIA: Cohort and case-control designs reporting on the mode of delivery and subsequent ectopic pregnancy. Two reviewers independently assessed the titles, abstracts, and full articles to identify eligible studies, using a standardised data collection form, and also assessed the study quality. Reference lists of the studies included were also cross-checked. DATA COLLECTION AND ANALYSIS: Odds ratios (ORs) were combined using a random-effect model to estimate the overall association between caesarean section delivery and the risk of subsequent ectopic pregnancy. MAIN RESULTS: Thirteen studies were included, which recruited a total of 61,978 women. Five studies reported adjustment for confounding factors, and the pooled OR of subsequent ectopic pregnancy following a caesarean section was 1.05 (95% CI 0.51-2.15). The removal of one study that reported outlier results yielded a pooled OR of 0.82 (95% CI 0.42-1.61). The pooled crude OR for all 13 studies was 1.36 (95% CI 0.99-1.88). AUTHOR'S CONCLUSIONS: This review found no evidence of an association between prior caesarean section delivery and the occurrence of a subsequent ectopic pregnancy, but the studies included were of poor or variable quality, and only a small number adjusted for potential confounding factors. Further research of a higher methodological quality is required to assess any potential association between mode of delivery and subsequent ectopic pregnancy.

Maternal serum cholesterol levels are elevated from the 1st trimester of pregnancy: a cross-sectional study.

Cholesterol is monitored in the non-pregnant adult population, where normal values are established. Although reported to be elevated in pregnancy, cholesterol is neither routinely measured nor treated. We aimed to investigate cholesterol levels throughout pregnancy and to establish reference values for cholesterol in healthy pregnant women. This was a cross-sectional analysis of serum cholesterol in healthy women with an uncomplicated singleton pregnancy. Pregnant women attending for antenatal care were recruited and cholesterol levels assayed at 12, 20, 28 and 36 weeks' gestation and on day 1-3 postpartum. A total of 222 women were recruited. The majority (95%) were white Irish, with a median age of 31 years (range 16-46). Median BMI was 25.9 kg/m2 (range 18-40) and 16% were smokers. Cholesterol levels were elevated in all trimesters of pregnancy, with median values from 1st trimester raised outside the non-pregnant adult range. High-density lipoprotein (HDL) levels ranged from 0.9 to 3.7 mmol/l and low-density lipoprotein (LDL) levels ranged from 1.3 to 6.1 mmol/l. Fasting, smoking and obesity did not have any significant effects on results. Total and LDL-cholesterol levels were raised throughout pregnancy. Levels were above non-pregnant adult ranges as early as the 1st trimester. The implications of this on fetus and mother are undetermined and deserve further investigation.