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.

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.

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.

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.

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.

A functional variant in ANGPT1 and the risk of pregnancies with hypertensive disorders and small-for-gestational-age infants.

Pregnancies complicated by pre-eclampsia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-eclampsia [P = 0.01, adjusted odds ratio (aOR), 0.5; 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5; 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7; 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6; 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-eclampsia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth.

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.

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.

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.

Antepartum haemorrhage of unknown origin and maternal cigarette smoking beyond the first trimester.

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 nonsmokers (7.4%, n = 30 vs 4.5%, n = 122; P = 0.01), but there was no difference between ceased smokers and nonsmokers (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 0.76­2.14), but vaginal bleeding in early pregnancy (adjusted OR = 2.98, 95% CI 2.12­4.18) and overweight/obesity (adjusted OR = 1.43, 95% CI 1.02­1.99) were independent risk factors. First trimester folic acid use was associated with a reduced risk (adjusted OR = 0.44, 95% CI 0.25­0.77). CONCLUSION: Smoking is not an independent risk factor for APHUO after adjustment for confounders, but other risk and protective factors have been identified.

Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.

A statistical model to identify differentially expressed proteins in 2D PAGE gels.

Two dimensional polyacrylamide gel electrophoresis (2D PAGE) is used to identify differentially expressed proteins and may be applied to biomarker discovery. A limitation of this approach is the inability to detect a protein when its concentration falls below the limit of detection. Consequently, differential expression of proteins may be missed when the level of a protein in the cases or controls is below the limit of detection for 2D PAGE. Standard statistical techniques have difficulty dealing with undetected proteins. To address this issue, we propose a mixture model that takes into account both detected and non-detected proteins. Non-detected proteins are classified either as (a) proteins that are not expressed in at least one replicate, or (b) proteins that are expressed but are below the limit of detection. We obtain maximum likelihood estimates of the parameters of the mixture model, including the group-specific probability of expression and mean expression intensities. Differentially expressed proteins can be detected by using a Likelihood Ratio Test (LRT). Our simulation results, using data generated from biological experiments, show that the likelihood model has higher statistical power than standard statistical approaches to detect differentially expressed proteins. An R package, Slider (Statistical Likelihood model for Identifying Differential Expression in R), is freely available at http://www.cebl.auckland.ac.nz/slider.php.

A proteomic approach identifies early pregnancy biomarkers for preeclampsia: novel linkages between a predisposition to preeclampsia and cardiovascular disease.

Preeclampsia (PE) is a common, potentially life-threatening pregnancy syndrome triggered by placental factors released into the maternal circulation, resulting in maternal vascular dysfunction along with activated inflammation and coagulation. Currently there is no screening test for PE. We sought to identify differentially expressed plasma proteins in women who subsequently develop PE that may perform as predictive biomarkers. In seven DIGE experiments, we compared the plasma proteome at 20 wk gestation in women who later developed PE with an appropriate birth weight for gestational age baby (n=27) or a small for gestational age baby (n=12) to healthy controls with uncomplicated pregnancies (n=57). Of the 49 differentially expressed spots associated with PE-appropriate for gestational age, PE-small for gestational age or both (p<0.05, false discovery rate corrected), 39 were identified by LC-MS/MS. Two protein clusters that accurately (>90%) classified women at risk of developing PE were identified. Immunoblots confirmed the overexpression of fibrinogen gamma chain and alpha-1-antichymotrypsin in plasma prior to PE. The proteins identified are involved in lipid metabolism, coagulation, complement regulation, extracellular matrix remodeling, protease inhibitor activity and acute-phase responses, indicating novel synergism between pathways involved in the pathogenesis of PE. Our findings are remarkably similar to recently identified proteins complexed to high-density lipoprotein and linked to cardiovascular disease.

Patterns of change in uterine artery Doppler studies between 20 and 24 weeks of gestation and pregnancy outcomes.

OBJECTIVES: To describe changes in mean uterine artery resistance index and bilateral notches between 20 and 24 weeks of gestation in healthy nulliparous women and to relate these changes to pregnancy outcome. METHODS: A total of 2,189 nulliparous participants in the Screening for Pregnancy Endpoints study had pregnancy outcomes compared between four uterine artery Doppler groups: normal at 20 and 24 weeks of gestation (group 1), normal at 20 weeks and abnormal at 24 weeks (group 2), abnormal at 20 weeks and normal at 24 weeks (group 3), and abnormal at both 20 and 24 weeks (group 4). Abnormal uterine Doppler was defined as 1) mean resistance index greater than the 90th centile; 2) bilateral notches; and 3) a combination of 1, 2, or both. The main outcomes were preeclampsia and small for gestational age (SGA) neonates (less than the 10th customized centile). RESULTS: Preeclampsia developed in 116 (5.3%) women, and 223 (10.2%) delivered SGA neonates. With abnormal Doppler defined as mean resistance index greater than the 90th centile, the rate of SGA increased across Doppler groups: group 1, 156 (8.4%); group 2, 13 (11%); group 3, 25 (19.5%); and group 4, 29 (35.4%) (P<.001). The rate of SGA was higher in group 3 compared with group 1. Preeclampsia differed among groups 1 (85 [4.6%]), 2 (9 [7.6%], 3 (7 [5.5%]), and 4 (15 [18.3%]) (P<.001). CONCLUSION: Pregnancy outcomes in women with abnormal uterine artery Doppler results at either 20 or 24 weeks were intermediate between those with normal or abnormal results at both time points. If overall test performance could be enhanced by the addition of clinical data, biomarkers, or both, we would recommend that 20 weeks is the most appropriate gestation in the second trimester to perform uterine artery Doppler studies. LEVEL OF EVIDENCE: II.

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.

Small-for-gestational-age infants classified by customized or population birthweight centiles: impact of gestational age at delivery.

OBJECTIVE: Evidence of placental disease and poor perinatal outcome is more common in infants who are small by customized centiles, compared with population centiles. Because preterm births are more likely to be associated with placental pathology, a greater proportion of preterm births are likely to be small for gestational age (SGA) by customized centiles, compared with population centiles. Our objective was to compare the proportion of infants classified as SGA by customized and population birthweight centiles at different gestational ages at delivery. STUDY DESIGN: This was a retrospective observational study of 17,855 nulliparous women delivering between 1992 and 1999 at National Women's Hospital, Auckland, New Zealand. The proportion of SGA infants (birthweight less than the 10th centile) classified by customized and population birthweight centiles delivering at less than 34 weeks, 34-36(+6) weeks, and 37 weeks or longer were compared. RESULTS: A total of 1847 infants (10.3%) were customized SGA, compared with 2111 (11.8%) who were population SGA (relative risk [RR] 0.9, 95% confidence interval [CI] 0.8 to 0.9). Of preterm deliveries less than 34 weeks (n = 392), 29.1% were customized SGA and 17.1% were population SGA (RR 1.7, 95% CI 1.3 to 2.2). Of deliveries at 34-36(+6) weeks (n = 946), 18.0% were customized SGA and 13.7% were population SGA (RR 1.3, 95% CI 1.1 to 1.6). The converse was observed at term (n = 16,517), 9.5% classified as customized SGA and 11.5% as population SGA (RR 0.82, 95% CI 0.77 to 0.87). Of all early preterm perinatal deaths (less than 34 weeks) 31 of 72 infants (43%) were customized SGA and 23 of 72 infants (32%) were population SGA. There were no perinatal deaths or deliveries less than 34 weeks in infants who were classified as SGA by population criteria only. CONCLUSION: Customized centiles classified more infants as SGA, compared with population centiles, in preterm births but not for term births in nulliparous women.

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.

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.