A prospective study of placental growth factor in twin pregnancy and development of a dichorionic twin pregnancy specific reference range.

OBJECTIVE: To develop a dichorionic twin pregnancy specific reference range for placental growth factor (PlGF), and to compare gestation-specific placental growth factor levels in twin pregnancies later complicated by pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction with control pregnancies. DESIGN: Prospective observational study. SETTING: Single large tertiary maternity unit in Ireland. POPULATION OR SAMPLE: Women with a twin pregnancy. METHODS: Consenting pregnant women, across a variety of gestations, had a single blood sample taken at one time-point only during their pregnancy. The plasma was initially biobanked and PlGF was measured later in batches using the point of care Triage® PlGF test. MAIN OUTCOME MEASURES: Development of pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction. RESULTS: Placental growth factor levels in uncomplicated dichorionic twin pregnancies were significantly lower in the women who later developed pre-eclampsia than in the controls at all gestational intervals. In those that later developed any hypertensive disorder of pregnancy, median PlGF was lower only in those recruited before 24 weeks of gestation, whereas in infants with a customised birthweight below the third centile, PlGF was lower only in those sampled after 24 weeks of gestation. CONCLUSIONS: Placental growth factor levels in twin pregnancy differ significantly between those women with a pregnancy that will later be complicated by pre-eclampsia and those that will not. This difference is present many weeks before clinical signs or symptoms of disease are present. Using cross-sectional values from uncomplicated twin pregnancies, we have developed a dichorionic twin pregnancy specific reference range for PlGF. TWEETABLE ABSTRACT: Placental growth factor levels in twin pregnancy differ significantly between women that will later develop pre-eclampsia and those that will not.

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.

Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial.

OBJECTIVES: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. METHODS: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. RESULTS: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056). CONCLUSIONS: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women.

OBJECTIVE: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2 ). DESIGN: Retrospective cohort study. SETTING: Multiple centres (in Australia, Ireland, New Zealand, and the UK). POPULATION: Five thousand five hundred and nineteen low-risk nulliparous pregnant women. METHODS: Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. MAIN OUTCOME MEASURES: Time to pregnancy and infertility. RESULTS: Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility. CONCLUSION: Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification. TWEETABLE ABSTRACT: Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia.

OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia. METHODS: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome. RESULTS: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation. CONCLUSION: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Enablers and barriers to physical activity in overweight and obese pregnant women: an analysis informed by the theoretical domains framework and COM-B model.

BACKGROUND: Obesity during pregnancy is associated with increased risk of gestational diabetes mellitus (GDM) and other complications. Physical activity is a modifiable lifestyle factor that may help to prevent these complications but many women reduce their physical activity levels during pregnancy. Interventions targeting physical activity in pregnancy are on-going but few identify the underlying behaviour change mechanisms by which the intervention is expected to work. To enhance intervention effectiveness, recent tools in behavioural science such as the Theoretical Domains Framework (TDF) and COM-B model (capability, opportunity, motivation and behaviour) have been employed to understand behaviours for intervention development. Using these behaviour change methods, this study aimed to identify the enablers and barriers to physical activity in overweight and obese pregnant women. METHODS: Semi-structured interviews were conducted with a purposive sample of overweight and obese women at different stages of pregnancy attending a public antenatal clinic in a large academic maternity hospital in Cork, Ireland. Interviews were recorded and transcribed into NVivo V.10 software. Data analysis followed the framework approach, drawing on the TDF and the COM-B model. RESULTS: Twenty one themes were identified and these mapped directly on to the COM-B model of behaviour change and ten of the TDF domains. Having the social opportunity to engage in physical activity was identified as an enabler; pregnant women suggested being active was easier when supported by their partners. Knowledge was a commonly reported barrier with women lacking information on safe activities during pregnancy and describing the information received from their midwife as 'limited'. Having the physical capability and physical opportunity to carry out physical activity were also identified as barriers; experiencing pain, a lack of time, having other children, and working prevented women from being active. CONCLUSION: A wide range of barriers and enablers were identified which influenced women's capability, motivation and opportunity to engage in physical activity with "knowledge" as the most commonly reported barrier. This study is a theoretical starting point in making a 'behavioural diagnoses' and the results will be used to inform the development of an intervention to increase physical activity levels among overweight and obese pregnant women.

The relationship between maternal 25-hydroxyvitamin D status in pregnancy and childhood adiposity and allergy: an observational study.

BACKGROUND: Vitamin D insufficiency (defined as <75 nmol l-1) is widespread among pregnant women around the world and has been proposed to influence offspring outcomes in childhood and into adult life, including adiposity and allergy. Disorders, including asthma and eczema, are on the rise among children. Our aim was to investigate the relationship between maternal 25-hydroxyvitamin D status in pregnancy and offspring adiposity, asthma and eczema in childhood. SUBJECTS AND METHODS: Maternal 25-hydroxyvitamin D concentrations were analysed in serum samples collected at 15 weeks' gestation from 1710 participants of the prospective Screening for Pregnancy Endpoints cohort study. The offspring of 1208 mothers were followed up at age 5-6 years. Data collected included height, weight, percentage body fat (PBF, measured by bioimpedance) and history of asthma and eczema. Multivariable analysis controlled for maternal body mass index (BMI), age and sex of the child and season of serum sampling. RESULTS: Complete data were available for 922 mother-child pairs. Each 10 nmol l-1 increase in maternal 25-hydroxyvitamin D concentration at 15 weeks' gestation was associated with a decrease in offspring PBF of 0.2% (95% confidence interval 0.04-0.36%, P=0.01) after adjustment for confounders but was not related to child BMI z-score. Maternal mean (±s.d.) 25-hydroxyvitamin D concentration was similar in children who did and did not have asthma (71.7±26.1 vs 73.3±27.1 nmol l-1, P=0.5), severe asthma (68.6±28.6 vs 73.3±26.8 nmol l-1, P=0.2) and eczema (71.9±27.0 vs 73.2±27.0 nmol l-1, P=0.5). CONCLUSIONS: The finding of a relationship between maternal vitamin D status and adiposity in childhood is important, particularly because vitamin D insufficiency in pregnancy is highly prevalent. The association between maternal vitamin D supplementation in pregnancy and adiposity in the offspring merits examination in randomised controlled trials.

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.

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): an international consortium of randomised placebo-controlled trials.

BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. DISCUSSION: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis. TRIAL REGISTRATIONS: New Zealand and Australia: ACTRN12612000584831 . Registered 30/05/2012. Canada: NCT02442492 . Registered 05/05/2015. Ireland: CT 900/572/1 . Registered 15/07/2015. The Netherlands: NCT02277132 . Registered 29/09/2014. United Kingdom: ISRCTN39133303 . Registered 31/07/2014.

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.

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.

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.

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.

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.

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.