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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., (© 2020 John Wiley & Sons Ltd.)

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., (© 2019 Royal College of Obstetricians and Gynaecologists.)

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/m 2 versus BMI ≥ 30 kg/m 2 )., 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., (© 2019 Royal College of Obstetricians and Gynaecologists.)

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., (© 2016 Royal College of Obstetricians and Gynaecologists.)

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., (© 2015 Royal College of Obstetricians and Gynaecologists.)

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., (© 2015 Royal College of Obstetricians and Gynaecologists.)

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., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objectives: To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women., Design: Predictive test accuracy study., Setting: Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE)., Methods: Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression., Main Outcome Measure: Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation)., Results: Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement., Conclusions: Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

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., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objective: To present 50 years of hospital-based maternal and perinatal outcomes in Sudan, and the role of an international collaboration with an Irish maternity hospital, over the period 2002-2009, in recent health-indicator improvements., Design: Retrospective descriptive study., Setting: Omdurman Maternity Hospital, Sudan., Population: All women who delivered at Omdurman Maternity Hospital, and their newborn infants, from July 1957 to October 2007, comprising 339 448 births., Methods: The original logbook data was extracted. Infant and maternal health indicators were calculated according to World Health Organization definitions., Main Outcomes Measures: Total annual births, maternal mortality ratio and maternal complications, neonatal mortality and stillbirth rates, and rates of delivery methods., Results: Total births increased 50-fold from 499 in 1958 to 24 913 in 2007. Significant reductions in morbidity and mortality began in the mid-1990s. From 2001 to 2007, maternal mortality fell from 329 to 36 per 100 000 live births: an 85% reduction. Stillbirth rates almost halved, from 35 to 19 per 1000 births in 2001 and 2007, respectively. Neonatal mortality rates remained largely static, at 24 per 1000 live births in 2007, but there is recent evidence of a decline., Conclusion: This hospital-based data offers a unique historical portrait of health outcomes in one of the largest maternity hospitals in Africa, and shows steady, sustained improvements in maternal, stillbirth and neonatal mortality rates since the 1990s. The partnership was associated with a number of positive infrastructural, educational, and staffing achievements. Whether it directly contributed to improved health outcomes has not been established., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Objective: To identify clinical and ultrasound variables associated with the birth of small-for-gestational-age (SGA) infants by customised centiles, subclassified according to whether their mothers were normotensive or developed hypertensive complications., Design: Prospective, multicentre cohort study., Setting: Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand, Adelaide, Australia, Manchester and London, UK, and Cork, Ireland., Population: The 3513 nulliparous participants of the SCOPE study., Methods: Women were interviewed at 15 ± 1 weeks, and had ultrasound growth measurements and umbilical and uterine Doppler studies at 20 ± 1 weeks. Variables associated with SGA infants were identified using logistic regression., Main Outcome Measures: Small for gestational age (i.e. a birthweight of less than the tenth customised centile), normotensive-SGA and hypertensive-SGA. Comparison groups for statistical analyses were non-SGA, normotensive non-SGA and hypertensive non-SGA., Results: Among 376 (10.7%) SGA infants, 281 (74.7%) were normotensive-SGA and 95 (25.3%) were hypertensive-SGA. Independent risk factors for normotensive-SGA were low maternal birthweight, low fruit intake pre-pregnancy, cigarette smoking, increasing maternal age, daily vigorous exercise, being a tertiary student, head and abdominal circumference of less than the tenth centile and increasing uterine artery Doppler indices at the 20-week scan. Protective factors were: high green leafy vegetable intake pre-pregnancy, and rhesus-negative blood group. Risk factors for hypertensive-SGA were conception by in vitro fertilisation, previous early pregnancy loss and femur length of less than tenth centile at the 20-week scan., Conclusions: Risk factors for infants who are SGA by customised centiles have been identified in a cohort of healthy nulliparous women. A number of these factors are modifiable; however, further studies are needed to replicate these findings., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)