Placental growth factor testing at 19-23 weeks of gestation as a guide to subsequent care in pregnancy: A prospective observational study.

OBJECTIVE: To determine whether serum placental growth factor (PlGF) at 19-23 weeks of gestation can improve the identification of risk for adverse outcomes. DESIGN: Prospective observational cohort study. SETTING: Two English maternity units. POPULATION: Unselected singleton pregnancies attending routine ultrasound at 19-23 weeks of gestation. METHODS: Outcomes ascertained by health record review. Diagnostic test properties evaluated clinical risk factors for pre-eclampsia (according to National Institute of Care Excellence) or fetal growth restriction (according to Royal College of Obstetricians and Gynaecologists), low PlGF at 19-23 weeks of gestation (<5th percentile) or both. MAIN OUTCOME MEASURES: Pre-eclampsia, gestational hypertension, stillbirth, birthweight below third percentile or neonatal intensive care unit (NICU) admission for ≥48 h. RESULTS: In 30 013 pregnancies, risk factors were present in 9941 (33.1%), low PlGF was present in 1501 (5.0%) and both ('two-stage' screening) were present in 547 (1.8%) pregnancies. Risk factors detected 41.7%-54.7% of adverse outcomes, and could not meaningfully revise the risk (all positive likelihood ratios, +LR, <5.0; all negative likelihood ratios, -LR, ≥0.2). Low PlGF detected 8.5%-17.4% of adverse outcomes, but meaningfully increased risks (other than NICU admission) associated with delivery <37 weeks of gestation (+LR = 5.03-15.55); all -LRs were ≥0.2. 'Two-stage' screening detected 4.2%-8.9% of adverse outcomes, with meaningful +LRs (6.28-18.61) at <37 weeks of gestation, except for NICU admission of ≥48 h, which had an +LR of 7.56 at <34 weeks of gestation; all -LRs were ≥0.2. No screening strategy meaningfully increased or decreased the detection of adverse outcome risk at term. CONCLUSIONS: Clinical risk factor screening has a high screen-positive rate and a poor detection of adverse outcomes. False positives cannot be reduced by PlGF testing at 19-23 weeks of gestation; therefore, this cannot be recommended as a useful strategy on its own.

The additive role of angiogenic markers for women with confirmed preeclampsia.

BACKGROUND: Hypertension complicates 2% to 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality globally. Given the prognostic role that angiogenic markers play in evaluation of patients with "suspected preeclampsia," the International Society for the Study of Hypertension in Pregnancy incorporated angiogenic imbalance into the 2021 definition of preeclampsia. As women with "suspected preeclampsia" are a heterogeneous group, with some already meeting the diagnostic criteria for preeclampsia, we evaluated whether the soluble fms-like tyrosine kinase-1/placental growth factor ratio adds prognostic value among these women. OBJECTIVE: This study aimed to assess the additive value of soluble fms-like tyrosine kinase-1/placental growth factor ratio when the diagnostic criteria for preeclampsia have already been met. STUDY DESIGN: This was a secondary analysis of a prospective cohort study of patients presenting to obstetrical triage with suspected preeclampsia at ≥20+0 weeks' gestation from July 2009 to June 2012 in Boston, United States. Clinicians were masked to soluble fms-like tyrosine kinase-1/placental growth factor ratio results. Clinical records were reviewed for maternal and neonatal care and outcomes. The value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio (≤38, >38, or >85) was assessed for identifying women at low or high risk of evolving into preeclampsia with severe features within 2 weeks of the triage visit, with preeclampsia with severe features being defined by the American College of Obstetricians and Gynecologists (2013 definition). Based on information in obstetrical triage, preeclampsia among triage patients was defined either by: (1) The International Society for the Study of Hypertension in Pregnancy "restrictive" criteria (ie, new-onset hypertension and proteinuria at ≥20 weeks), or (2) The International Society for the Study of Hypertension in Pregnancy "broad" maternal criteria (ie, new-onset hypertension with proteinuria or one/more relevant maternal end-organ complications). RESULTS: Of 1043 patients included, 459 presented at 20+0 to 34+6 weeks and 584 at ≥35+0 weeks. In triage, 25.8% of women with "suspected preeclampsia" already met the preeclampsia criteria based on the International Society for the Study of Hypertension in Pregnancy broad criteria and 22.0% based on the restrictive criteria. In separate multivariable analyses adjusted for gestational age, a soluble fms-like tyrosine kinase-1/placental growth factor ratio >38 was independently associated with preeclampsia with severe features within 2 weeks even after adjusting for preeclampsia diagnosis in obstetrical triage, whether that preeclampsia were defined restrictively (odds ratio, 15.62; 95% confidence interval, 8.91-27.40) or broadly (odds ratio, 14.56; 95% confidence interval, 8.30-25.56). A soluble fms-like tyrosine kinase-1/placental growth factor ratio ≤38 was good at ruling out development of preeclampsia with severe features within 2 weeks among all patients and among those meeting the restrictive or broad definitions of preeclampsia (negative likelihood ratios, ≤0.16), driven by performance of the ratio before 35 weeks (ie, negative likelihood ratio ≤0.12). A soluble fms-like tyrosine kinase-1/placental growth factor ratio >85 was good at ruling-in preeclampsia with severe features within 2 weeks among women with suspected preeclampsia, either before (positive likelihood ratio, 8.20) or after 35 weeks (positive likelihood ratio, 6.00) and fair at ruling-in preeclampsia with severe features within 2 weeks when preeclampsia had already been confirmed in patients at <35 weeks (restrictively positive likelihood ratio, 3.48, or broadly positive likelihood ratio, 3.40). CONCLUSION: Our findings support the prognostic value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio among patients with confirmed preeclampsia, particularly to identify those both likely and unlikely to progress toward the development of severe features in the next 2 weeks and those who may be most appropriate for expectant and potentially outpatient care. Our findings support the incorporation of angiogenic imbalance into the definition of preeclampsia, particularly at 20-34+0 weeks.

Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre-eclampsia.

OBJECTIVE: To examine the effect of self-declared race on serum placental growth factor (PlGF) and sFlt-1/PlGF ratio and the impact on pre-eclampsia (PE) prediction. DESIGN: Prospective observational study. SETTING: Two UK maternity hospitals. POPULATION: 29 035 women with singleton pregnancies attending a routine 35+0 to 36+6 weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE. METHODS: The predictive performance of PlGF and sFlt-1/PlGF for PE in minority racial groups (versus white) was examined. MAIN OUTCOME MEASURE: Delivery with PE. RESULTS: Compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut-off corresponding to a screen-positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut-off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut-off in sFlt-1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient-specific risks. CONCLUSION: Screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

BACKGROUND: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. METHODS: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. RESULTS: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10-4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10-7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10-7). CONCLUSIONS: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication.

Impact of new definitions of preeclampsia at term on identification of adverse maternal and perinatal outcomes.

BACKGROUND: Any definition of preeclampsia should identify women and babies at greatest risk of adverse outcomes. OBJECTIVE: This study aimed to investigate the ability of the American College of Obstetricians and Gynecologists and International Society for the Study of Hypertension in Pregnancy definitions of preeclampsia at term gestational age (≥37 0/7 weeks) to identify adverse maternal and perinatal outcomes. STUDY DESIGN: In this prospective cohort study at 2 maternity hospitals in England, women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment that included history; ultrasonographic estimated fetal weight; Doppler measurements of the pulsatility index in the uterine, umbilical, and fetal middle cerebral arteries; and serum placental growth factor-to-soluble fms-like tyrosine kinase-1 ratio. Obstetrical records were examined for all women with chronic hypertension and those who developed new-onset hypertension, with preeclampsia (de novo or superimposed on chronic hypertension) defined in 5 ways: traditional, based on new-onset proteinuria; American College of Obstetricians and Gynecologists 2013 definition; International Society for the Study of Hypertension in Pregnancy maternal factors definition; International Society for the Study of Hypertension in Pregnancy maternal factors plus fetal death or fetal growth restriction definition, defined according to the 35 0/7 to 36 6/7 weeks' gestation scan as either estimated fetal weight <3rd percentile or estimated fetal weight at the 3rd to 10th percentile with any of uterine artery pulsatility index >95th percentile, umbilical artery pulsatility index >95th percentile, or middle cerebral artery pulsatility index <5th percentile; and International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance definition, defined as placental growth factor <5th percentile or soluble fms-like tyrosine kinase-1-to-serum placental growth factor >95th percentile. Detection rates for outcomes of interest (ie, severe maternal hypertension, major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal unit admission ≥48 hours, and birthweight <10th percentile) were compared using the chi-square test, and P<.05 was considered significant. RESULTS: Among 15,248 singleton pregnancies, the identification of women with preeclampsia varied by definition: traditional, 15 of 281 (1.8%; 248); American College of Obstetricians and Gynecologists, 15 of 326 (2.1%; 248); International Society for the Study of Hypertension in Pregnancy maternal factors, 15 of 400 (2.6%; 248); International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, 15 of 434 (2.8%; 248); and International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, 15 of 500 (3.3%; 248). Compared with the traditional definition of preeclampsia, the International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance best identified the adverse outcomes: severe hypertension (40.6% [traditional] vs 66.9% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P<.0001], 59.2% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.004], 56.2% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.013], 46.1% [American College of Obstetricians and Gynecologists, P=.449]); P<.0001); composite maternal severe adverse event (72.2% [traditional] vs 100% for all others; P=.046); composite of perinatal mortality and morbidity (46.9% [traditional] vs 71.1% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P=.002], 62.2% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.06], 59.8% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.117], 49.4% [American College of Obstetricians and Gynecologists, P=.875]); neonatal unit admission for ≥48 hours (51.4% [traditional] vs 73.4% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P=.001], 64.5% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors, P=.070], 60.7% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.213], 53.3% [American College of Obstetricians and Gynecologists, P=.890]); birthweight <10th percentile (40.5% [traditional] vs 78.7% [International Society for the Study of Hypertension in Pregnancy maternal-fetal factors plus angiogenic imbalance, P<.0001], 70.1% [International Society for the Study of Hypertension in Pregnancy maternal-fetal, P<.0001], 51.3% [International Society for the Study of Hypertension in Pregnancy maternal factors, P=.064], 46.3% [American College of Obstetricians and Gynecologists, P=.349]). CONCLUSION: Our findings present an evidence base for the broad definition of preeclampsia. Our data suggest that compared with a traditional definition, a broad definition of preeclampsia can better identify women and babies at risk of adverse outcomes. Compared with the American College of Obstetricians and Gynecologists definition, the more inclusive International Society for the Study of Hypertension in Pregnancy definition of maternal end-organ dysfunction seems to be more sensitive. The addition of uteroplacental dysfunction to the broad definition optimizes the identification of women and babies at risk, particularly when angiogenic factors are included.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Timing of delivery in a high-risk obstetric population: a clinical prediction model.

BACKGROUND: The efficacy of antenatal corticosteroid treatment for women with threatened preterm birth depends on timely administration within 7 days before delivery. We modelled the probability of delivery within 7 days of admission to hospital among women presenting with threatened preterm birth, using routinely collected clinical characteristics. METHODS: Data from the Canadian Perinatal Network (CPN) were used, 2005-11, including women admitted to hospital with preterm labour, preterm pre-labour rupture of membranes, short cervix without contractions, or dilated cervix or prolapsed membranes without contractions at preterm gestation. Women with fetal anomaly, intrauterine fetal demise, twin-to-twin transfusion syndrome, and quadruplets were excluded. Logistic regression was undertaken to create a predictive model that was assessed for its calibration capacity, stratification ability, and classification accuracy (ROC curve). RESULTS: We included 3012 women admitted at 24-28 weeks gestation, or readmitted at up to 34 weeks gestation, to 16 tertiary-care CPN hospitals. Of these, 1473 (48.9%) delivered within 7 days of admission. Significant predictors of early delivery included maternal age, parity, gestational age at admission, smoking, preterm labour, prolapsed membranes, preterm pre-labour rupture of membranes, and antepartum haemorrhage. The area under the ROC curve was 0.724 (95% CI 0.706-0.742). CONCLUSION: We propose a useful tool to improve prediction of delivery within 7 days after admission among women with threatened preterm birth. This information is important for optimal corticosteroid treatment.

The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured Review.

OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) mortality prediction model in pregnant and recently pregnant women receiving critical care in low-, middle-, and high-income countries during the study period (1985-2015), using a structured literature review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based Medicine Reviews, searched for articles published between 1985 and 2015. STUDY SELECTION: Twenty-five studies (24 publications), of which two were prospective, were included in the analyses. Ten studies were from high-income countries (HICs), and 15 were from low- and middle-income countries (LMICs). Median study duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU admission complicates 0.48% of deliveries, and pregnant and recently pregnant women account for 1.49% of ICU admissions. One quarter were admitted while pregnant, three quarters of these for an obstetric indication and for a median of three days. The median APACHE II score was 10.9, with a median APACHE II-predicted mortality of 16.6%. Observed mortality was 4.6%, and the median standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were more frequently admitted with a medical comorbidity but were less likely to die than were women in LMICs. CONCLUSION: The APACHE II score consistently overestimates mortality risks for pregnant and recently pregnant women receiving critical care, whether they reside in HICs or LMICs. There is a need for a pregnancy-specific outcome prediction model for these women.

Preventing deaths due to the hypertensive disorders of pregnancy.

In this chapter, taking a life cycle and both civil society and medically oriented approach, we will discuss the contribution of the hypertensive disorders of pregnancy (HDPs) to maternal, perinatal and newborn mortality and morbidity. Here we review various interventions and approaches to preventing deaths due to HDPs and discuss effectiveness, resource needs and long-term sustainability of the different approaches. Societal approaches, addressing sustainable development goals (SDGs) 2.2 (malnutrition), 3.7 (access to sexual and reproductive care), 3.8 (universal health coverage) and 3c (health workforce strengthening), are required to achieve SDGs 3.1 (maternal survival), 3.2 (perinatal survival) and 3.4 (reduced impact of non-communicable diseases (NCDs)). Medical solutions require greater clarity around the classification of the HDPs, increased frequency of effective antenatal visits, mandatory responses to the HDPs when encountered, prompt provision of life-saving interventions and sustained surveillance for NCD risk for women with a history of the HDPs.

Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial immunoassays.

OBJECTIVE: Placental growth factor and soluble Fms-like tyrosine kinase-1 may be potential diagnostic markers of preeclampsia. We compared performances of 2 immunoassays, the Triage placental growth factor assay and the Elecsys soluble Fms-like tyrosine kinase-1/placental growth factor ratio in diagnosing preeclampsia. STUDY DESIGN: A single site, case-control study of 44 patients with preeclampsia and 84 matched normal pregnant controls. Samples were collected at the time of diagnosis. Assays were performed according to product inserts. RESULTS: Both assays had optimal performance in diagnosing early-onset preeclampsia with area under the receiver operating characteristic curves of 0.99 (Triage: 100% sensitivity, 96% specificity; Elecsys: 64% sensitivity, 100% specificity for early-onset preeclampsia). Reassignment of the Elecsys cutoff for a positive test based on receiver operating characteristic curves increased sensitivity to 92%. CONCLUSION: Using product insert cutoffs, Triage appears to have greater sensitivity at only a small reduction in specificity compared with Elecsys in the diagnosis of early-onset preeclampsia. A different cutoff may improve Elecsys sensitivity.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

Our patients do not need endocarditis prophylaxis for genitourinary tract procedures: insights from the 2007 American Heart Association guidelines.

The 2007 American Heart Association guidelines for the prevention of infective endocarditis have dramatically reduced both the types of eligible procedures and the types of eligible cardiac lesions that require prophylaxis. Antibiotic prophylaxis to prevent infective endocarditis is not indicated for any patient undergoing obstetric and/or gynaecological procedures, not even for patients with underlying cardiac lesions with the highest risk of developing complications from endocarditis. This sharp departure from previously published guidelines relies on the recognition that endocarditis is more likely to develop from "randomly occurring" bacteremia (e.g., from brushing teeth) than from invasive procedures and that antibiotic prophylaxis has not been proven to be effective. A short discussion on enterococcal infections associated to obstetric and gynaecological procedures and therapeutic implications is presented.

Instituting surveillance guidelines and adverse outcomes in preeclampsia.

OBJECTIVE: To assess the incidence of combined adverse maternal and perinatal outcomes in women with preeclampsia before and after introducing standardized assessment and surveillance. METHODS: This study was a preintervention (retrospective) compared with a postintervention (prospective) cohort comparison in a single-tertiary, perinatal unit that included women admitted to hospital with preeclampsia. We interrogated an existing retrospective 24-month database and then introduced the guidelines, assessing the incidence of the combined adverse maternal and perinatal outcomes for 41 months (September 2003 through February 2007). Tests of organ (dys)function were performed at least as often as on the day of admission, admission day +1, every Monday and Thursday, day of delivery, and delivery day +1. All data were checked for errors. The combined maternal outcome was maternal death or one or more of hepatic failure, hematoma, or rupture, Glasgow coma score of less than 13, stroke, at least two seizures, cortical blindness, need for positive inotrope support, myocardial infarction, infusion of any third antihypertensive, renal dialysis, renal transplantation, at least 50% FIO(2) for greater than 1 hour, intubation, or transfusion of at least 10 units of blood products. The combined perinatal outcome was perinatal or infant mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, grade III/IV intraventricular hemorrhage, cystic periventricular leukomalacia, or stage 3-5 retinopathy of prematurity. RESULTS: Two hundred ninety-five and 405 women were in the preintervention and postintervention cohorts, respectively. The incidence of adverse maternal outcome fell (5.1% to 0.7%; Fisher P<.001; odds ratio 0.14, 95% confidence interval 0.04-0.49). Perinatal outcomes did not change. CONCLUSION: Standardized surveillance of women with preeclampsia was associated with reduced maternal risk.

Preeclampsia and future cardiovascular risk.

Pregnancy is a metabolic and vascular 'stress test' for women and those who 'fail' are at increased risk of long-term cardiovascular complications. Specifically, women who develop preeclampsia (and/or other manifestations of placental dysfunction) are at increased risk of coronary heart disease, stroke and cardiovascular disease in general. The risk is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery. Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and their absolute risk of cardiovascular disease in the short term is very low. However, perhaps having a placentally complicated pregnancy affords women the opportunity to personalize risk and take action. Action is needed. The fact that we, as a population, are getting heavier and more sedentary is an urgent public health issue. The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle changes, in addition to smoking cessation. Engaging women of child-bearing age who may be motivated by a complicated pregnancy would be very valuable, from a public health perspective, given the prevalence and importance of cardiovascular disease in women, and the central role of the woman as caregiver to children, spouses and other family members.

Variations in early and intermediate neonatal outcomes for inborn infants admitted to a Canadian NICU and born of hypertensive pregnancies.

OBJECTIVE: To determine whether neonatal intensive care unit (NICU) outcomes vary by centre for inborn neonates of hypertensive pregnancies and, if so, whether that variation might be related to between-centre variations in obstetric practice. METHODS: The study comprised a prospective cohort of 13 505 singleton neonates admitted to 17 Canadian NICUs. Adjusting for potential confounders, we used multivariate regression to analyze the relation between centre of delivery and 6 dependent variables: (1) Apgar score < 7 at 5 minutes; (2) Score of Neonatal Acute Physiology-II (SNAP-II) score > or = 10; (3) neonatal death; (4) neonatal death or morbidity (owing to bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH], necrotizing enterocolitis [NEC], persistent ductus arteriosus [PDA], or periventricular leukomalacia [PVL]); (5) BPD alone; and (6) major neonatal morbidity (that is, at least one of IVH, PVL, NEC, or PDA). NICU practices known to influence these outcomes were included in the modelling for neonatal death and neonatal morbidity. In a sensitivity analysis for practice variation, antenatal steroid exposure was both included and excluded in each regression. RESULTS: For 5 of the 6 dependent variables, we identified between-centre variation that was not explained solely by variation in antenatal corticosteroid use. Adjusted odds ratios varied from 0.11 to 5.6 (the reference centre was the median rate of the adverse outcome). CONCLUSIONS: In the pregnancy hypertension setting, between-centre variations in practice are associated with variations in neonatal physiology and survival. For infants admitted to NICU, the obstetric management of hypertensive pregnancies appears to have an effect on both short- and medium-term neonatal outcomes, even after correction for NICU management.