How Do Home and Clinic Blood Pressure Readings Compare in Pregnancy?

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

Antenatal risk factors associated with neonatal morbidity in large-for-gestational-age infants: an international prospective cohort study.

INTRODUCTION: Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large-for-gestational-age infants. MATERIAL AND METHODS: Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large-for-gestational-age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self-reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity. RESULTS: Among term pregnancies, prevalence of large-for-gestational-age infants was 9.3% (491/5255), with 11.8% (58/491) prevalence of neonatal morbidity. Random glucose at 20 weeks (odds ratio 1.52; 95% confidence interval 1.17-1.97, per 1 mmol/L increase) and no regular physical activity at 20 weeks (odds ratio 3.93; 95% confidence interval 1.75-8.83) were associated with increased risk of neonatal morbidity after adjustment for birthweight, gestational age at delivery and gestational diabetes. The increased risk associated with higher glucose levels was not evident in women with regular physical activity or without obesity. CONCLUSIONS: Regular physical activity in mid-pregnancy is associated with lower risk for neonatal morbidity in large-for-gestational-age infants and seems to offer protection against the increased risk associated with higher maternal glucose levels.

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers.

OBJECTIVE: Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks' with ultrasound parameters at 20±1 weeks' gestation. METHODS: Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. RESULTS: 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks' clinical variables, 15±1 weeks' clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks' were: 0.63 (0.59-0.67), 0.64 (0.60-0.68) and 0.69 (0.66-0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57-0.66), 0.61 (0.56-0.66) and 0.68 (0.64-0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70-0.82), 0.80 (0.75-0.86) and 0.84 (0.78-0.89) with minimal change in the Training datasets. CONCLUSION: Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry.

Clinical and biochemical factors associated with preeclampsia in women with obesity.

OBJECTIVE: To compare early pregnancy clinical and biomarker risk factors for later development of preeclampsia between women with obesity (body mass index, BMI ≥30 kg/m2 ) and those with a normal BMI (20-25 kg/m2 ). METHODS: In 3,940 eligible nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study, a total of 53 biomarkers of glucose and lipid metabolism, placental function, and known markers of preeclampsia were measured at 14 to 16 weeks' gestation. Logistic regression was performed to identify clinical and biomarker risk factors for preeclampsia in women with and without obesity. RESULTS: Among 834 women with obesity and 3,106 with a normal BMI, 77 (9.2%) and 105 (3.4%) developed preeclampsia, respectively. In women with obesity, risk factors included a family history of thrombotic disease, low plasma placental growth factor, and higher uterine artery resistance index at 20 weeks. In women with a normal BMI, a family history of preeclampsia or gestational hypertension, mean arterial blood pressure, plasma endoglin and cystatin C, and uterine artery resistance index were associated with preeclampsia, while high fruit intake was protective. CONCLUSIONS: Women with obesity and a normal BMI have different early pregnancy clinical and biomarker risk factors for preeclampsia.

SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.

This guideline is an evidence based, practical clinical approach to the management of Hypertensive Disorders of Pregnancy. Since the previous SOMANZ guideline published in 2008, there has been significant international progress towards harmonisation of definitions in relation to both the diagnosis and management of preeclampsia and gestational hypertension. This reflects increasing knowledge of the pathophysiology of these conditions, as well as their clinical manifestations. In addition, the guideline includes the management of chronic hypertension in pregnancy, an approach to screening, advice regarding prevention of hypertensive disorders of pregnancy, and discussion of recurrence risks and long term risk to maternal health. The literature reviewed included the previous SOMANZ Hypertensive Disorders of Pregnancy guideline from 2008 and its reference list, plus all other published National and International Guidelines on this subject. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT), National Institute for Health and Care Excellence (NICE) Evidence Search, and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2007 and March, 2014.

Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies.

OBJECTIVES: To compare the prevalence and predictors of alcohol use in multiple cohorts. DESIGN: Cross-cohort comparison of retrospective and prospective studies. SETTING: Population-based studies in Ireland, the UK, Australia and New Zealand. PARTICIPANTS: 17,244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of alcohol use pre-pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort. RESULTS: Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1-2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70). CONCLUSIONS: Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates.

Exploration and confirmation of factors associated with uncomplicated pregnancy in nulliparous women: prospective cohort study.

STUDY QUESTION: Which variables at 15 and 20 weeks' gestation, particularly those amenable to modification before pregnancy, are associated with a subsequent uncomplicated pregnancy? SUMMARY ANSWER: Normalising body mass index, increasing fruit intake before pregnancy, reducing blood pressure, stopping misuse of drugs, and being in paid employment are all associated with subsequent uncomplicated pregnancy outcomes.

Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia.

Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58-0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Exploration and confirmation of factors associated with uncomplicated pregnancy in nulliparous women: prospective cohort study.

OBJECTIVE: To identify factors at 15 and 20 weeks' gestation associated with a subsequent uncomplicated pregnancy. DESIGN: Prospective international multicentre observational cohort study. SETTING: Auckland, New Zealand and Adelaide, Australia (exploration and local replication dataset) and Manchester, Leeds, and London, United Kingdom, and Cork, Republic of Ireland (external confirmation dataset). PARTICIPANTS: 5628 healthy nulliparous women with a singleton pregnancy. MAIN OUTCOME MEASURE: Uncomplicated pregnancy, defined as a normotensive pregnancy delivered at >37 weeks' gestation, resulting in a liveborn baby not small for gestational age, and the absence of any other significant pregnancy complications. In a stepwise logistic regression the comparison group was women with a complicated pregnancy. RESULTS: Of the 5628 women, 3452 (61.3%) had an uncomplicated pregnancy. Factors that reduced the likelihood of an uncomplicated pregnancy included increased body mass index (relative risk 0.74, 95% confidence intervals 0.65 to 0.84), misuse of drugs in the first trimester (0.90, 0.84 to 0.97), mean diastolic blood pressure (for each 5 mm Hg increase 0.92, 0.91 to 0.94), and mean systolic blood pressure (for each 5 mm Hg increase 0.95, 0.94 to 0.96). Beneficial factors were prepregnancy fruit intake at least three times daily (1.09, 1.01 to 1.18) and being in paid employment (per eight hours' increase 1.02, 1.01 to 1.04). Detrimental factors not amenable to alteration were a history of hypertension while using oral contraception, socioeconomic index, family history of any hypertensive complications in pregnancy, vaginal bleeding during pregnancy, and increasing uterine artery resistance index. Smoking in pregnancy was noted to be a detrimental factor in the initial two datasets but did not remain in the final model. CONCLUSIONS: This study identified factors associated with normal pregnancy through adoption of a novel hypothesis generating approach, which has shifted the emphasis away from adverse outcomes towards uncomplicated pregnancies. Although confirmation in other cohorts is necessary, this study implies that individually targeted lifestyle interventions (normalising maternal weight, increasing prepregnancy fruit intake, reducing blood pressure, stopping misuse of drugs) may increase the likelihood of normal pregnancy outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12607000551493.

Association between maternal alcohol consumption in early pregnancy and pregnancy outcomes.

OBJECTIVE: To investigate the association between alcohol consumption and binge drinking before and during early pregnancy and adverse pregnancy outcomes. METHODS: We used data from 5,628 nulliparous pregnant participants recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study. Participants were interviewed at 15 weeks of gestation and information on alcohol intake before pregnancy and until the time of interview was obtained using a standardized questionnaire. Alcohol intake was classified as occasional (1-2 units per week), low (3-7 units per week), moderate (8-14 units per week), and heavy (greater than 14 units per week). Binge alcohol consumption was defined as consumption of 6 or more alcohol units in one session. RESULTS: Of the 5,628 participants, 1,090 (19%) reported occasional alcohol consumption, 1,383 (25%) low alcohol consumption, 625 (11%) moderate alcohol consumption, and 300 (5%) heavy alcohol consumption. Overall, 1,905 (34%) participants reported binge alcohol consumption in the 3 months before pregnancy, and 1,288 (23%) of these participants reported binge alcohol consumption during the first 15 weeks of pregnancy. Participants who consumed occasional to heavy amounts of alcohol in early pregnancy did not have altered odds of a small-for-gestational-age neonate, reduced birth weight, preeclampsia, or spontaneous preterm birth. Similarly, those who binge drank in early pregnancy did not have altered odds of these adverse pregnancy outcomes. CONCLUSION: Alcohol consumption in early pregnancy was prevalent in this nulliparous cohort. There was no association between alcohol consumption before 15 weeks of gestation and small for gestational age, reduced birth weight, preeclampsia, or spontaneous preterm birth. LEVEL OF EVIDENCE: : II.

Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth.

STUDY QUESTION: Do women with a previous miscarriage or termination of pregnancy have an increased risk of spontaneous preterm birth and is this related to previous cervical dilatation and curettage? SUMMARY ANSWER: A single previous pregnancy loss (termination or miscarriage) managed by cervical dilatation and curettage is associated with a greater risk of SpPTB. WHAT IS KNOWN ALREADY: Miscarriage affects ∼20% of pregnancies and as many as a further 20% of pregnancies undergo termination. STUDY DESIGN, SIZE, DURATION: We utilized data from 5575 healthy nulliparous women with singleton pregnancies recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study performed between November 2004 and January 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome was spontaneous preterm birth (defined as spontaneous preterm labour or preterm premature rupture of membranes (PPROM) resulting in preterm birth <37 weeks' gestation). Secondary outcomes included PPROM, small for gestational age, birthweight, pre-eclampsia and placental abruption. MAIN RESULTS AND THE ROLE OF CHANCE: Women with previous pregnancy loss (miscarriage or termination) were compared with those with no previous pregnancy loss. There were 4331 (78%) women who had no previous pregnancy loss, 974 (17.5%) who had one early previous pregnancy loss, 249 (4.5%) who had two and 21 (0.5%) who had three or four losses. Women with two to four previous losses, but not those with a single loss, had an increased risk of spontaneous preterm birth (adjusted OR 2.12; 95% CI 1.55, 2.90) and/or placental abruption (adjusted OR 2.30; 95% CI 1.36, 3.89) compared with those with no previous pregnancy. A single previous miscarriage or termination of pregnancy where the management involved cervical dilatation and curettage was associated with an increased risk of spontaneous preterm birth (adjusted OR 1.64; 95% CI 1.08, 2.50; 6% absolute risk and adjusted OR 1.83; 95% CI 1.35, 2.48; 7% absolute risk, respectively) compared with those with no previous pregnancy losses. This is in contrast with women with a single previous miscarriage or termination managed non-surgically who showed no increase risk (adjusted OR 0.86; 95% CI 0.38, 1.94; 3.4% absolute risk and adjusted OR 0.87; 95% CI 0.69, 1.12; 3.8% absolute risk, respectively). LIMITATIONS, REASONS FOR CAUTION: Although every effort was made to record accurate previous pregnancy data, it was not feasible to confirm the history and management of previous pregnancy loss by hospital records. This may have introduced recall bias. WIDER IMPLICATIONS OF THE FINDINGS: This large prospective cohort study of healthy nulliparous women has demonstrated that women with either a previous miscarriage or termination of pregnancy were at increased risk of spontaneous preterm birth if they were managed by procedures involving cervical dilatation and curettage. However, overall, women with a single pregnancy loss did not have an increased risk of having any other of the adverse pregnancy outcomes examined. In contrast, two to four previous pregnancy losses were associated with an increased risk of having a pregnancy complicated by spontaneous preterm birth and/or placental abruption. Research is required to determine whether non-surgical management of miscarriage or termination of pregnancy should be advocated over surgical treatment. STUDY FUNDING/COMPETING INTEREST(S): New Zealand: New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council; Evelyn Bond Fund, Auckland District Health Board Charitable Trust. Australia: Premier's Science and Research Fund, South Australian Government. Ireland: Health Research Board. Leeds: Cerebra Charity, Carmarthen. Manchester: National Health Service NEAT Grant; Manchester Biotechnology and Biological Sciences Research Council; University of Manchester Proof of Concept Funding. King's College London: Guy's and St Thomas' Charity. King's College London and Manchester: Tommy's-The Baby Charity. TRIAL REGISTRATION NUMBER: N/A.

Clinical prediction in early pregnancy of infants small for gestational age by customised birthweight centiles: findings from a healthy nulliparous cohort.

OBJECTIVE: Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants. METHODS: 5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15 ± 1 weeks' gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20 ± 1 weeks'. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated. RESULTS: 633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15 ± 1 weeks' included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥ 3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥ 80. Recreational walking ≥ 4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10(th) centile and increasing uterine artery Doppler resistance at 20 ± 1 weeks' were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively. CONCLUSION: Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension.

Integrated proteomics pipeline yields novel biomarkers for predicting preeclampsia.

Preeclampsia, a hypertensive pregnancy complication, is largely unpredictable in healthy nulliparous pregnant women. Accurate preeclampsia prediction in this population would transform antenatal care. To identify novel protein markers relevant to the prediction of preeclampsia, a 3-step mass spectrometric work flow was applied. On selection of candidate biomarkers, mostly from an unbiased discovery experiment (19 women), targeted quantitation was used to verify and validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma specimens collected at 19 to 21 weeks' gestation from 100 women who later developed preeclampsia and 200 women without preeclampsia recruited from Australia and New Zealand. Protein levels (n=25), age, and blood pressure were then analyzed using logistic regression to identify multimarker models (maximum 6 markers) that met predefined criteria: sensitivity ≥50% at 20% positive predictive value. These 44 algorithms were then tested in an independent European cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of preeclampsia cases in the training and validation sets; the detection rate for preterm preeclampsia cases was 80%. Validated models combine insulin-like growth factor acid labile subunit and soluble endoglin, supplemented with maximally 4 markers of placental growth factor, serine peptidase inhibitor Kunitz type 1, melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive performances were maintained when exchanging mass spectrometry measurements with ELISA measurements for insulin-like growth factor acid labile subunit. In conclusion, we demonstrated that biomarker combinations centered on insulin-like growth factor acid labile subunit have the potential to predict preeclampsia in healthy nulliparous women.

Perinatal outcomes in large infants using customised birthweight centiles and conventional measures of high birthweight.

BACKGROUND: Large-for-gestational-age (LGA) or macrosomic infants are associated with adverse maternal and neonatal outcomes. It is unclear if these associations are stronger using customised birthweight centiles. We compared outcomes between term infants defined macrosomic by birthweight >4000 g (Macro(4000) ) or LGA by population centiles (LGA(pop) ) with those defined LGA by customised centiles (LGA(cust) ). METHODS: This is a prospective cohort study of 2668 term nulliparous women recruited into the Screening for Pregnancy Endpoints (SCOPE) study centres in Auckland, New Zealand and Adelaide, Australia. Maternal (caesarean delivery, postpartum haemorrhage) and infant (severe neonatal morbidity/mortality and admission to neonatal intensive care) outcomes in Macro(4000) and LGA groups were compared with appropriate-for-gestational-age infants by customised centiles using logistic regression. RESULTS: Customised centiles defined fewer infants as LGA (10.3% LGA(cust) , 14.8% Macro(4000) , 11.2% LGA(pop) ). However customised centiles showed stronger association with adverse outcomes. Pre-labour and intrapartum caesarean section were increased twofold in LGA(cust) pregnancies, including those that were not Macro(4000) or LGA(pop) . Postpartum haemorrhage was increased twofold in mothers of LGA(cust) infants only when infants were also LGA(pop) . Severe neonatal morbidity/mortality or admission to neonatal intensive care was increased twofold in LGA(cust) who were also either Macro(4000) or LGA(pop) . Importantly 52.3% of Macro(4000) and 25.5% of LGA(pop) infants were AGA(cust) and not at increased risk of most adverse maternal or neonatal outcomes. CONCLUSIONS: The use of customised centiles are more strongly associated with adverse birth outcomes and its use should be considered in the definition of LGA.

Risk factors for preterm birth in an international prospective cohort of nulliparous women.

OBJECTIVES: To identify risk factors for spontaneous preterm birth (birth <37 weeks gestation) with intact membranes (SPTB-IM) and SPTB after prelabour rupture of the membranes (SPTB-PPROM) for nulliparous pregnant women. DESIGN: Prospective international multicentre cohort. PARTICIPANTS: 3234 healthy nulliparous women with a singleton pregnancy, follow up was complete in 3184 of participants (98.5%). RESULTS: Of the 3184 women, 156 (4.9%) had their pregnancy complicated by SPTB; 96 (3.0%) and 60 (1.9%) in the SPTB-IM and SPTB-PPROM categories, respectively. Independent risk factors for SPTB-IM were shorter cervical length, abnormal uterine Doppler flow, use of marijuana pre-pregnancy, lack of overall feeling of well being, being of Caucasian ethnicity, having a mother with diabetes and/or a history of preeclampsia, and a family history of low birth weight babies. Independent risk factors for SPTB-PPROM were shorter cervical length, short stature, participant's not being the first born in the family, longer time to conceive, not waking up at night, hormonal fertility treatment (excluding clomiphene), mild hypertension, family history of recurrent gestational diabetes, and maternal family history of any miscarriage (risk reduction). Low BMI (<20) nearly doubled the risk for SPTB-PPROM (odds ratio 2.64; 95% CI 1.07-6.51). The area under the receiver operating characteristics curve (AUC), after internal validation, was 0.69 for SPTB-IM and 0.79 for SPTB-PPROM. CONCLUSION: The ability to predict PTB in healthy nulliparous women using clinical characteristics is modest. The dissimilarity of risk factors for SPTB-IM compared with SPTB-PPROM indicates different pathophysiological pathways underlie these distinct phenotypes. TRIAL REGISTRATION: ACTR.org.au ACTRN12607000551493.

Patterns of vaginal bleeding during the first 20 weeks of pregnancy and risk of pre-eclampsia in nulliparous women: results from the SCOPE study.

OBJECTIVE: To describe patterns of vaginal bleeding in the first 20 weeks of pregnancy and evaluate the association between patterns of bleeding and risk of subsequent pre-eclampsia in nulliparous women. DESIGN: 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: Healthy nulliparous women (n= 3431). METHODS: Logistic regression was used to assess the association between bleeding characteristics and pre-eclampsia while controlling for known determinants of pre-eclampsia. MAIN OUTCOME MEASURES: Preeclampsia, defined as gestational hypertension with proteinuria or any multi-system complication of preeclampsia. Four bleeding variables were evaluated: any bleeding during the first 20 weeks; maximal bleeding intensity; duration of bleeding; and number of bleeding episodes. RESULTS: Of the 3431 women enrolled, 780 (23%) experienced vaginal bleeding during the first 20 weeks of pregnancy. Risk of pre-eclampsia was not associated with the presence or absence of bleeding (adjusted odds ratio (ORa) 0.96, 95% confidence interval (95% CI) 0.67-1.38). Analyses confined to women with vaginal bleeding showed that any bleeding episode of five or more consecutive days, compared with shorter episodes, increased risk of pre-eclampsia approximately twofold (ORa 2.15, 95% CI 1.01-4.57), as did multiple compared with single episodes of bleeding (ORa 2.33, 95% CI 1.16-4.67). CONCLUSIONS: Bleeding is a common complication during the first 20 weeks of nulliparous pregnancy, and the presence or absence of vaginal bleeding is not a determinant of subsequent pre-eclampsia. Among women with vaginal bleeding, consideration of the bleeding pattern, in terms of intensity, duration and frequency, appears to be informative with respect to pre-eclampsia risk.

A Bayesian model for classifying all differentially expressed proteins simultaneously in 2D PAGE gels.

BACKGROUND: Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is commonly used to identify differentially expressed proteins under two or more experimental or observational conditions. Wu et al (2009) developed a univariate probabilistic model which was used to identify differential expression between Case and Control groups, by applying a Likelihood Ratio Test (LRT) to each protein on a 2D PAGE. In contrast to commonly used statistical approaches, this model takes into account the two possible causes of missing values in 2D PAGE: either (1) the non-expression of a protein; or (2) a level of expression that falls below the limit of detection. RESULTS: We develop a global Bayesian model which extends the previously described model. Unlike the univariate approach, the model reported here is able treat all differentially expressed proteins simultaneously. Whereas each protein is modelled by the univariate likelihood function previously described, several global distributions are used to model the underlying relationship between the parameters associated with individual proteins. These global distributions are able to combine information from each protein to give more accurate estimates of the true parameters. In our implementation of the procedure, all parameters are recovered by Markov chain Monte Carlo (MCMC) integration. The 95% highest posterior density (HPD) intervals for the marginal posterior distributions are used to determine whether differences in protein expression are due to differences in mean expression intensities, and/or differences in the probabilities of expression. CONCLUSIONS: Simulation analyses showed that the global model is able to accurately recover the underlying global distributions, and identify more differentially expressed proteins than the simple application of a LRT. Additionally, simulations also indicate that the probability of incorrectly identifying a protein as differentially expressed (i.e., the False Discovery Rate) is very low. The source code is available at https://github.com/stevenhwu/BIDE-2D.