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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 <10th 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. [ABSTRACT FROM AUTHOR]

In our search for early biomarkers for the pregnancy complicationssmall for gestational age (SGA) and preeclampsia (PE) we analysed plasma from 19-21 weeks gestation in women recruited into the SCOPE study, a prospective cohort of nulliparous women, by differential in gel electrophoresis (DIGE). DIGE revealed the differential expression of clusterin levels and its isoforms in top6-depleted plasma of women who delivered an SGA infant but remained normotensive (SGA-NT; N = 8) compared to healthy women with an uncomplicated pregnancy outcome (Controls, N = 8). Immunosorbent enzyme-linked assay (ELISA) showed that compared to plasma clusterin levels from healthy controls [71.1 (SD 12.4) µg/mL, n = 39], clusterin was decreased in SGA-NT [58.3 (SD 11.7), N = 20, P < 0.0001], increased in women with SGA and PE [81.5 (SD 14.8), N = 20, P < 0.01], but similar in PE alone [71.2 (SD 9.4)g/ml, P = 1.0]. Screening for clusterin levels and/or its different isoformsmay be useful in mid-pregnancy to identify women who subsequently develop SGA but remain normotensive or who develop preeclampsia with SGA. [ABSTRACT FROM AUTHOR]

Background Antepartum haemorrhage of unknown origin ( APHUO) is associated with preterm birth and perinatal mortality. Aim To determine whether smoking beyond the first trimester of pregnancy was an independent risk factor for APHUO. Methods Rates of APHUO were compared between non-smokers and smokers, and non-smokers and ceased smokers. Participants were healthy nulliparous women recruited to the Screening for Pregnancy Endpoints ( SCOPE) prospective cohort study in New Zealand, Australia, Ireland and United Kingdom. Logistic regression was used to compare adjusted odds ratio, 95% confidence intervals ( OR, 95% CI) of APHUO between continued smokers and non-smokers, adjusting for possible confounders. Results Of the 3513 participants, 77.9% ( n = 2737) were non-smokers, 10.6% ( n = 371) ceased in the first trimester and 11.5% ( n = 405) continued smoking beyond the first trimester. APHUO rates were higher in smokers than non-smokers (7.4%, n = 30 vs 4.5%, n = 122; P = 0.01), but there was no difference between ceased smokers and non-smokers (4.3%, n = 16 vs 4.5%, n = 122; P = 0.90). Smoking was no longer significantly associated with APHUO after adjustment for confounders (adjusted OR = 1.28, 95% CI 0.76-2.14), but vaginal bleeding in early pregnancy (adjusted OR = 2.98, 95% CI 2.12-4.18) and overweight/obesity (adjusted OR = 1.43, 95% CI 1.02-1.99) were independent risk factors. First trimester folic acid use was associated with a reduced risk (adjusted OR = 0.44, 95% CI 0.25-0.77). Conclusion Smoking is not an independent risk factor for APHUO after adjustment for confounders, but other risk and protective factors have been identified. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy. Methods The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15±1 weeks' gestation and at 20±1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6-24), Perceived Stress Scale score (PSS, range 0-30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0-30 or categories a-c) and behavioural responses to pregnancy score (limiting/resting [range 0-20] and all-or-nothing [range 0-28]). Results During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15±1 and 20±1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]). Conclusion This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial. [ABSTRACT FROM AUTHOR]

Objective. To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women. Methods. Individual risk scores based on clinical risk factors were calculated using logistic regression and validated in 1687 women with obesity in first pregnancy, chronic hypertension, or previous preeclampsia. Results. The risk of preeclampsia varied from 7% in obese primiparae without hypertension to 30% when previous preeclampsia and chronic hypertension occurred together. A prediction model incorporating these risk factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks' gestation. Conclusion. Multiple clinical risk factors increase the risk of preeclampsia and SGA. [ABSTRACT FROM AUTHOR]

To date, there is no reliable test to identify women in early pregnancy at risk of developing preeclampsia. Difference gel electrophoresis (DIGE) identified the plasma proteins vitronectin (VN) and high-molecular-weight kininogen (HK) in association with preeclampsia. In a longitudinal proteomics study, the plasma of preeclamptic patients (n = 6) was compared to healthy control participants (n = 6) before the onset of preeclampsia (week 20) and at the time of presentation with clinical disease (weeks 33-36). The 75-kd single-chain VN molecule increased 1.6- to 1.9-fold in preeclampsia, whereas the 65-kd moiety of the 2-chain VN molecule decreased 1.5- to 1.7-fold compared to healthy controls (P < .05). Immunoblots revealed differences in proteolytic processing of VN and/or HK in women who develop preeclampsia or preeclampsia further complicated by small-for-gestational-age. Vitronectin and HK may prove to be useful as early markers of fibrinolytic activity and neutrophil activation, which are known to be associated with preeclampsia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to investigate the relationship between blood pressure that is measured with the automated blood pressure monitor, Omron HEM-705CP (Omron Corporation, Tokyo, Japan), and mercury sphygmomanometry in normotensive and preeclamptic pregnant women. STUDY DESIGN: Healthy pregnant women (n = 101 women) underwent mercury and home Omron HEM705CP monitor blood pressure measurements at 10 to 14, 19 to 22, 27 to 30, and 35 to 37 weeks of gestation and 5 to 9 weeks after delivery. After routine mercury blood pressure recordings that were taken by midwives, women with preeclampsia (n = 45 women) measured their own blood pressure using an Omron HEM-705CP monitor (n = 212 recordings). In the longitudinal cohort, mean ± 2 SD were calculated for blood pressure levels throughout pregnancy. Individual variation in home Omron minus office mercury throughout pregnancy was determined. In preeclampsia, back-to-back blood pressure measurements by the two methods were correlated and quantified as being within 5, 10, and 15 mm Hg. Bland-Altman plots were calculated, and the sensitivity of the Omron HEM-705CP monitor to detect hypertension that was identified by mercury sphygmomanometry was evaluated. RESULTS: At 10 to 14, 19 to 22, 27 to 30, and 35 to 37 weeks of gestation, the upper limits for normal systolic blood pressure levels with the use of home Omron HEM-705CP monitor measurements were 132, 130, 133, and 138 mm Hg and for diastolic blood pressure levels were 82, 79, 81, and 88 mm Hg, respectively. For women who were normotensive and had preeclampsia (although group mean blood pressure values by mercury sphygmomanometry and Omron HEM-705CP monitor were similar), there were marked individual differences (≤40 mm Hg) between the devices. In preeclampsia, paired Omron monitor and mercury systolic and diastolic blood pressure levels were within 5, 10, and 15 mm Hg in 47%, 73%, and 82%, and 56%, 78%, and 92%, respectively. The Omron... [ABSTRACT FROM AUTHOR]

Summary: Background: Maternal obesity has been implicated in the origins of childhood obesity through a suboptimal environment in‐utero. Objective: We examined relationships of maternal early pregnancy body mass index (BMI), overweight/obesity, and plasma biomarkers of obesity, inflammation, insulin resistance, and placental function with measures of childhood BMI and adiposity. Methods: BMI z‐score, sum of skinfold thicknesses (SST), body fat percentage (BFP, by bioelectrical impedance), and waist, arm, and hip circumferences were measured in 1173 6‐year‐old children of nulliparous pregnant women in the Screening for Pregnancy Endpoints (SCOPE) study, New Zealand. Relationships of maternal early pregnancy (15 weeks' gestation) BMI and biomarkers with these childhood anthropometric measures were assessed by linear regression, with appropriate adjustment. Results: 28.1% of mothers were classified as overweight and 10.1% with obesity; compared with normal weight mothers, the BFP of their children were 5.3% higher (0.16 SD [95% CI, 0.04‐0.29] p = .01) and 7.8% higher (0.27 [0.08‐0.47] p = .006) with comparable values for BMI z‐score and arm, waist, and hip circumferences. Early pregnancy maternal BMI and plasma placental growth factor (PlGF) were associated with higher child's SST, BMI z‐score, hip circumference, and BFP. None of the metabolic or inflammatory maternal biomarkers were associated with childhood obesity. Conclusion: In this contemporary large prospective cohort study with extensive maternal/childhood phenotyping and a high prevalence of maternal overweight/obesity, we found independent relationships of maternal early pregnancy BMI with childhood BMI and adiposity; similar associations were observed with PlGF, which may imply a role for placenta function in the developmental programming of childhood obesity risk. [ABSTRACT FROM AUTHOR]

The article discusses a prospective cohort study for determining the factors associated with uncomplicated pregnancy in nulliparous women. The factors associated with subsequent uncomplicated pregnancy outcomes include normalised body mass index, reduced blood pressure and increased fruit intake before pregnancy. The article discusses how the identified factors can be used in the development of interventions to increase normal pregnancy outcomes.

The article focuses on a prospective cohort study related to the feasibility of clinical risk factors in the prediction of pre-eclampsia in nulliparous women. The study found that the capability of clinical phenotype in predicting pre-eclampsia in women is moderate. It informs that nulliparous women with singleton pregnancy were examined during the study. A chart depicting clinical risk factors for pre-eclampsia at 14-16 weeks' gestation in logistic regression model is also presented.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules. Study design: CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n =8) in comparison to controls (n =8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n =14) and prior to the development of pre-eclampsia (at 20 weeks’ gestation, n =20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n =34). Results: In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261)pg/ml, P =0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144)pg/ml, P =0.09]. Conclusion: Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia. [Copyright &y& Elsevier]

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, I 2 >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.

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.

Objectives: To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated., Design: Prospective multicentre cohort., Setting: Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland., Participants: 3572 "healthy" nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%)., Main Outcome Measure: Pre-eclampsia defined as ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks' gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37(+0) weeks' gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia., Results: Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks' gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively., Conclusions: The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

Objectives: To compare pregnancy outcomes between women who stopped smoking in early pregnancy and those who either did not smoke in pregnancy or continued to smoke., Design: Prospective cohort study., Setting: Auckland, New Zealand and Adelaide, Australia., Participants: 2504 nulliparous women participating in the Screening for Pregnancy Endpoints (SCOPE) study grouped by maternal smoking status at 15 (+/-1) week's gestation., Main Outcome Measures: Spontaneous preterm birth and small for gestational age infants (birth weight <10th customised centile). We compared odds of these outcomes between stopped smokers and non-smokers, and between current smokers and stopped smokers, using logistic regression, adjusting for demographic and clinical risk factors., Results: 80% (n=1992) of women were non-smokers, 10% (n=261) had stopped smoking, and 10% (n=251) were current smokers. We noted no differences in rates of spontaneous preterm birth (4%, n=88 v 4%, n=10; adjusted odds ratio 1.03, 95% confidence interval l0.49 to 2.18; P=0.66) or small for gestational age infants (10%, n=195 v 10%, n=27; 1.06, 0.67 to 1.68; P=0.8) between non-smokers and stopped smokers. Current smokers had higher rates of spontaneous preterm birth (10%, n=25 v 4%, n=10; 3.21, 1.42 to 7.23; P=0.006) and small for gestational age infants (17%, n=42 v 10%, n=27; 1.76, 1.03 to 3.02; P=0.03) than stopped smokers., Conclusion: In women who stopped smoking before 15 weeks' gestation, rates of spontaneous preterm birth and small for gestational age infants did not differ from those in non-smokers, indicating that these severe adverse effects of smoking may be reversible if smoking is stopped early in pregnancy.