Individual, Independent, and Joint Associations of Toxic Metals and Manganese on Hypertensive Disorders of Pregnancy: Results from the MIREC Canadian Pregnancy Cohort.

BACKGROUND: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. OBJECTIVES: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. METHODS: Metal concentrations were analyzed in first and third trimester maternal blood (n=1,560). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. RESULTS: Each doubling of third trimester Pb (RR=1.54; 95% CI: 1.06, 2.22) and first trimester blood As (RR=1.25; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As (RR=3.40; 95% CI: 1.40, 8.28) and Mn (RR=0.63; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension (RR=1.31; 95% CI: 0.60, 2.85) or preeclampsia (RR=0.92; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. DISCUSSION: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. https://doi.org/10.1289/EHP10825.

Perinatal Factors Associated With Breastfeeding Trends After Preterm Birth <29 Weeks Gestation: Can We Predict Early Discontinuation?

OBJECTIVE: To determine the rates and perinatal factors associated with initiation and early discontinuation of breastfeeding among very preterm neonates. METHODS: This was a retrospective cohort study of very preterm infants (<29 weeks gestation) admitted to 2 regional Level III neonatal intensive care units (NICUs) from January 1, 2015, to December 31, 2019. A national neonatal database was used to evaluate initiation and continuation rates of breastfeeding and associated perinatal factors. Stored nutrition profiles and delivery record books were used to determine feeding volumes associated with continuation of breastfeeding to hospital discharge for a subgroup of infants at a single site. Descriptive and inferential statistics were used to present the results between groups, and logistic regression modeling was used to calculate crude and adjusted odds ratios (OR) and 95% CI. RESULTS: Of 391 eligible neonates, 84% initiated breastfeeding but only 38% continued to discharge. Interestingly, frequency of breastfeeding initiation (P < 0.001) and continuation (P < 0.001) declined over the study period. After adjustment for confounders, younger maternal age, earlier gestational age, cigarette smoking, and multiparity were significantly associated with early discontinuation of breastfeeding prior to hospital discharge. Early discontinuation of breastfeeding was also related to lower volumes of breastmilk by day 7 of life (P = 0.004). CONCLUSION: Very preterm neonates are at high risk for non-initiation and early discontinuation of breastfeeding. The early postnatal period represents a critical time to establish breastmilk volumes, and the identification of key perinatal risk factors allows for early and targeted breastfeeding support.

Guideline No. 426: Hypertensive Disorders of Pregnancy: Diagnosis, Prediction, Prevention, and Management.

OBJECTIVE: This guideline was developed by maternity care providers from obstetrics and internal medicine. It reviews the diagnosis, evaluation, and management of the hypertensive disorders of pregnancy (HDPs), the prediction and prevention of preeclampsia, and the postpartum care of women with a previous HDP. TARGET POPULATION: Pregnant women. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in these guidelines may reduce the incidence of the HDPs, particularly preeclampsia, and associated adverse outcomes. EVIDENCE: A comprehensive literature review was updated to December 2020, following the same methods as for previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines, and references were restricted to English or French. To support recommendations for therapies, we prioritized randomized controlled trials and systematic reviews (if available), and evaluated substantive clinical outcomes for mothers and babies. VALIDATION METHODS: The authors agreed on the content and recommendations through consensus and responded to peer review by the SOGC Maternal Fetal Medicine Committee. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).The Board of the SOGC approved the final draft for publication. INTENDED USERS: All health care providers (obstetricians, family doctors, midwives, nurses, and anesthesiologists) who provide care to women before, during, or after pregnancy.

Directive clinique no 426 : Troubles hypertensifs de la grossesse : Diagnostic, prédiction, prévention et prise en charge.

OBJECTIF: La présente directive a été élaborée par des fournisseurs de soins de maternité en obstétrique et en médecine interne. Elle aborde le diagnostic, l'évaluation et la prise en charge des troubles hypertensifs de la grossesse, la prédiction et la prévention de la prééclampsie ainsi que les soins post-partum des femmes avec antécédent de trouble hypertensif de la grossesse. POPULATION CIBLE: Femmes enceintes. BéNéFICES, RISQUES ET COûTS: La mise en œuvre des recommandations de la présente directive devrait réduire l'incidence des troubles hypertensifs de la grossesse, en particulier la prééclampsie, et des issues défavorables associées. DONNéES PROBANTES: La revue exhaustive de la littérature a été mise à jour en tenant compte des nouvelles données probantes jusqu'en décembre 2020 et en suivant la même méthodologie que pour la précédente directive de la Société des obstétriciens et gynécologues du Canada (SOGC) sur les troubles hypertensifs de la grossesse. La recherche s'est limitée aux articles publiés en anglais ou en français. Les recommandations relatives aux traitements s'appuient d'abord sur les essais cliniques randomisés et les revues systématiques (lorsque disponibles), ainsi que sur l'évaluation des résultats cliniques substantiels chez les mères et les bébés. MéTHODES DE VALIDATION: Les auteurs se sont entendus sur le contenu et les recommandations par consensus et ont répondu à l'examen par les pairs du comité de médecine fœto-maternelle de la SOGC. Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE) et se sont gardé l'option de désigner certaines recommandations par la mention « bonne pratique ¼. Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). Le conseil d'administration de la SOGC a approuvé la version définitive aux fins de publication. PROFESSIONNELS CIBLES: Tous les fournisseurs de soins de santé (obstétriciens, médecins de famille, sages-femmes, infirmières et anesthésistes) qui prodiguent des soins aux femmes avant, pendant ou après la grossesse.

Guideline No. 426: Hypertensive disorders of pregnancy: diagnosis, prediction, prevention, and management

This guideline was developed by maternity care providers from obstetrics and internal medicine. It reviews the diagnosis, evaluation, and management of the hypertensive disorders of pregnancy (HDPs), the prediction and prevention of preeclampsia, and the postpartum care of women with a previous HDP. Implementation of the recommendations in these guidelines may reduce the incidence of the HDPs, particularly preeclampsia, and associated adverse outcomes. A comprehensive literature review was updated to December 2020, following the same methods as for previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines, and references were restricted to English or French. To support recommendations for therapies, we prioritized randomized controlled trials and systematic reviews (if available), and evaluated substantive clinical outcomes for mothers and babies. The authors agreed on the content and recommendations through consensus and responded to peer review by the SOGC Maternal Fetal Medicine Committee. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).The Board of the SOGC approved the final draft for publication. All health care providers (obstetricians, family doctors, midwives, nurses, and anesthesiologists) who provide care to women before, during, or after pregnancy.

Early prenatal use of a multivitamin diminishes the risk for inadequate vitamin D status in pregnant women: results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study.

BACKGROUND: Reports on the adequacy of vitamin D status of pregnant women are not available in Canada. OBJECTIVES: The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada. METHODS: Pregnant women (≥18 years) from 6 provinces (2008-2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n = 1905) and third trimesters (n = 1649) and at delivery (n = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test. RESULTS: In the first trimester, 93.4% (95% CI: 92.3%-94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25-0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42-3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02-1.89). CONCLUSIONS: The results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women.

Dynamic placenta-on-a-chip model for fetal risk assessment of nanoparticles intended to treat pregnancy-associated diseases.

Pregnant women often have to take medication either for pregnancy-related diseases or for previously existing medical conditions. Current maternal medications pose fetal risks due to off target accumulation in the fetus. Nanoparticles, engineered particles in the nanometer scale, have been used for targeted drug delivery to the site of action without off-target effects. This has opened new avenues for treatment of pregnancy-associated diseases while minimizing risks on the fetus. It is therefore instrumental to study the potential transfer of nanoparticles from the mother to the fetus. Due to limitations of in vivo and ex vivo models, an in vitro model mimicking the in vivo situation is essential. Placenta-on-a-chip provides a microphysiological recapitulation of the human placenta. Here, we reviewed the fetal risks associated with current therapeutic approaches during pregnancy, analyzed the advantages and limitations of current models used for nanoparticle assessment, and highlighted the current need for using dynamic placenta-on-a-chip models for assessing the safety of novel nanoparticle-based therapies during pregnancy.

Association of perfluoroalkyl substances with gestational hypertension and preeclampsia in the MIREC study.

BACKGROUND: Perfluoroalkyl substances (PFAS) have been linked with a number of developmental, reproductive, hepatic, and cardiovascular health outcomes. However, the evidence for an association between PFAS and hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) is equivocal and warrants further investigation. OBJECTIVES: To examine the relationship between background levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) and the development of gestational hypertension or preeclampsia in a Canadian pregnancy cohort. We also explored the potential for effect modification according to fetal sex. METHODS: Maternal plasma samples were collected in the first trimester from participants in the MIREC study and were analyzed for PFOA, PFOS, and PFHxS. Blood pressure was measured during each trimester. Gestational hypertension and preeclampsia were defined using the Society of Obstetricians and Gynaecologists of Canada guidelines. Logistic regression models were used to derive adjusted odds ratios (OR) and 95% confidence intervals (CI) for associations between PFAS concentrations (per doubling of concentration as well as according to tertiles) and gestational hypertension or preeclampsia. Linear mixed models were used to examine the association between PFAS concentrations and changes in blood pressure throughout pregnancy. RESULTS: Data from 1739 participants were analyzed. 90% of women were normotensive throughout pregnancy, 7% developed gestational hypertension without preeclampsia, and 3% developed preeclampsia. In the full analyses, neither PFOA nor PFOS were associated with gestational hypertension or preeclampsia. However, each doubling of PFHxS plasma concentration was associated with higher odds of developing preeclampsia (OR = 1.32; 95% CI: 1.03, 1.70). In addition, participants in the highest PFHxS tertile (1.4-40.0 µg/L) had higher odds of developing preeclampsia relative to those in the lowest tertile (OR = 3.06; 95% CI: 1.27, 7.39). In stratified analyses, this effect was only apparent among women carrying a female fetus (OR = 4.90; 95% CI: 1.02, 22.3). However, among women carrying a male fetus, both PFOS and PFHxS were associated with gestational hypertension, but not preeclampsia. Higher plasma concentrations of all three PFAS were associated with increases in diastolic blood pressure throughout pregnancy, and PFOA and PFHxS were also associated with systolic blood pressure. Discrepant findings were similarly revealed in analyses stratified by fetal sex. CONCLUSIONS: Higher levels of PFHxS were associated with the development of preeclampsia, but not gestational hypertension. Neither PFOA nor PFOS were associated with either outcome. However, we show, for the first time, that fetal sex may modify these associations, a finding which warrants replication and further study.

Management of non-severe pregnancy hypertension - A summary of the CHIPS Trial (Control of Hypertension in Pregnancy Study) research publications.

The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women with chronic (75%) or gestational (25%) hypertension. Pre-eclampsia developed in 48%; women remained on their allocated BP control and delivered an average of two weeks later. 'Less tight' control (target diastolic BP 100 mmHg) achieved BP that was 6/5mmHg higher (p < 0.001) than 'tight' control (target diastolic 85 mmHg, BP achieved 133/85 mmHg). 'Less tight' (vs. 'tight') control resulted in similar adverse perinatal outcomes (31.5% vs. 30.7%; p = 0.84) that balanced birthweight < 10th percentile (16.1% vs. 19.8%; p = 0.14) against preterm birth (35.6% vs. 31.5%; p = 0.18). 12-month follow-up revealed no compelling evidence for developmental programming of child growth. However, 'less tight' (vs. 'tight') control resulted in more severe maternal hypertension (40.6% vs. 27.5%; p < 0.001), and more women with platelets < 100 × 109/L (4.3% vs. 1.6%; p = 0.02) or symptomatic elevated liver enzymes (4.3% vs. 1.8%; p = 0.03), with no difference in serious maternal complications (3.7% vs. 2.0%; p = 0.17). Labetalol was the drug of choice. Methyldopa did not result in inferior outcomes. Post-hoc, severe hypertension, independent of pre-eclampsia, was associated with heightened increased risk of adverse outcomes, and in 'less tight' control, of serious maternal complications. At no gestational age at initiation of BP control was 'less tight' superior to 'tight'. Women in both groups were equally satisfied with care. 'Less tight' control tended to be more expensive by CAD$6000 (p =0.07) based on neonatal care costs. Collectively, CHIPS publications have provided evidence that women with non-severe pregnancy hypertension should receive 'tight' BP control achieved by a simple algorithm.

The Association of Inadequate and Intensive Prenatal Care With Maternal, Fetal, and Infant Outcomes: A Population-Based Study in Manitoba, Canada.

OBJECTIVE: Little is known about how prenatal care influences health outcomes in Canada. The objective of this study was to examine the association of prenatal care utilization with maternal, fetal, and infant outcomes in Manitoba. METHODS: This retrospective cohort study conducted at the Manitoba Centre for Health Policy investigated all deliveries of singleton births from 2004-2005 to 2008-2009 (N = 67 076). The proportion of women receiving inadequate, intermediate/adequate, and intensive prenatal care was calculated. Multivariable logistic regression was used to examine the association of inadequate and intensive prenatal care with maternal and fetal-infant health outcomes, health care use, and maternal health-related behaviours. RESULTS: The distribution of prenatal care utilization was 11.6% inadequate, 84.4% intermediate/adequate, and 4.0% intensive. After adjusting for sociodemographic factors and maternal health conditions, inadequate prenatal care was associated with increased odds of stillbirth, preterm birth, low birth weight, small for gestational age (SGA), admission to the NICU, postpartum depressive/anxiety disorders, and short interpregnancy interval to next birth. Women with inadequate prenatal care had reduced odds of initiating breastfeeding or having their infant immunized. Intensive prenatal care was associated with reduced odds of stillbirth, preterm birth, and low birth weight and increased odds of postpartum depressive/anxiety disorders, initiation of breastfeeding, and infant immunization. CONCLUSION: Inadequate prenatal care was associated with increased odds of several adverse pregnancy outcomes and lower likelihood of health-related behaviours, whereas intensive prenatal care was associated with reduced odds of some adverse pregnancy outcomes and higher likelihood of health-related behaviours. Ensuring women receive adequate prenatal care may improve pregnancy outcomes.

CHIPS-Child: Testing the developmental programming hypothesis in the offspring of the CHIPS trial.

OBJECTIVES: As a follow-up to the CHIPS trial (Control of Hypertension In Pregnancy Study) of 'less tight' (versus 'tight') control of maternal blood pressure in pregnancy, CHIPS-Child investigated potential developmental programming of maternal blood pressure control in pregnancy, by examining measures of postnatal growth rate and hypothalamic-pituitary adrenal (HPA) axis activation. METHODS: CHIPS follow-up was extended to 12 ±â€¯2 months corrected post-gestational age for anthropometry (weight, length, head/waist circumference). For eligible children with consent for a study visit, we collected biological samples (hair/buccal samples) to evaluate HPA axis function (hair cortisol levels) and epigenetic change (DNA methylation analysis of buccal cells). The primary outcome was 'change in z-score for weight' between birth and 12 ±â€¯2 mos. Secondary outcomes were hair cortisol and genome-wide DNA methylation status. RESULTS: Of 683 eligible babies, 183 (26.8%) were lost to follow-up, 83 (12.2%) declined, 3 (0.4%) agreed only to ongoing contact, and 414 (60.6%) consented. 372/414 (89.9%) had weight measured at 12mos. In 'less tight' (vs. 'tight') control, the primary outcome was similar [-0.26 (-0.53, +0.01); p = 0.14, padjusted = 0.06]; median (95% confidence interval) hair cortisol (N = 35 samples) was lower [-496 (-892, -100) ng/g; p = 0.02], and buccal swab DNA methylation (N = 16 samples) was similar. No differences in growth rate could be demonstrated up to 5 years. CONCLUSIONS: Results demonstrate no compelling evidence for developmental programming of growth or the HPA axis. Clinicians should look to the clinical findings of CHIPS to guide practice. Researchers should seek to replicate these findings and extend outcomes to paediatric blood pressure and neurodevelopment.

Inequities in utilization of prenatal care: a population-based study in the Canadian province of Manitoba.

BACKGROUND: Ensuring high quality and equitable maternity services is important to promote positive pregnancy outcomes. Despite a universal health care system, previous research shows neighborhood-level inequities in utilization of prenatal care in Manitoba, Canada. The purpose of this population-based retrospective cohort study was to describe prenatal care utilization among women giving birth in Manitoba, and to determine individual-level factors associated with inadequate prenatal care. METHODS: We studied women giving birth in Manitoba from 2004/05-2008/09 using data from a repository of de-identified administrative databases at the Manitoba Centre for Health Policy. The proportion of women receiving inadequate prenatal care was calculated using a utilization index. Multivariable logistic regressions were used to identify factors associated with inadequate prenatal care for the population, and for a subset with more detailed risk information. RESULTS: Overall, 11.5% of women in Manitoba received inadequate, 51.0% intermediate, 33.3% adequate, and 4.1% intensive prenatal care (N = 68,132). Factors associated with inadequate prenatal care in the population-based model (N = 64,166) included northern or rural residence, young maternal age (at current and first birth), lone parent, parity 4 or more, short inter-pregnancy interval, receiving income assistance, and living in a low-income neighborhood. Medical conditions such as multiple birth, hypertensive disorders, antepartum hemorrhage, diabetes, and prenatal psychological distress were associated with lower odds of inadequate prenatal care. In the subset model (N = 55,048), the previous factors remained significant, with additional factors being maternal education less than high school, social isolation, and prenatal smoking, alcohol, and/or illicit drug use. CONCLUSION: The rate of inadequate prenatal care in Manitoba ranged from 10.5-12.5%, and increased significantly over the study period. Factors associated with inadequate prenatal care included geographic, demographic, socioeconomic, and pregnancy-related factors. Rates of inadequate prenatal care varied across geographic regions, indicating persistent inequities in use of prenatal care. Inadequate prenatal care was associated with several individual indicators of social disadvantage, such as low income, education less than high school, and social isolation. These findings can inform policy makers and program planners about regions and populations most at-risk for inadequate prenatal care and assist with development of initiatives to reduce inequities in utilization of prenatal care.

The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is Severe Hypertension Just an Elevated Blood Pressure?

To determine whether clinical outcomes differed by occurrence of severe hypertension in the international CHIPS trial (Control of Hypertension in Pregnancy Study), adjusting for the interventions of "less tight" (target diastolic blood pressure [dBP] 100 mm Hg) versus "tight" control (target dBP 85 mm Hg). In this post-hoc analysis of CHIPS data from 987 women with nonsevere nonproteinuric preexisting or gestational hypertension, mixed effects logistic regression was used to compare the following outcomes according to occurrence of severe hypertension, adjusting for allocated group and the influence of baseline factors: CHIPS primary (perinatal loss or high-level neonatal care for >48 hours) and secondary outcomes (serious maternal complications), birth weight <10th percentile, preeclampsia, delivery at <34 or <37 weeks, platelets <100×109/L, elevated liver enzymes with symptoms, maternal length of stay ≥10 days, and maternal readmission before 6 weeks postpartum. Three hundred and thirty-four (34.1%) women in CHIPS developed severe hypertension that was associated with all outcomes examined except for maternal readmission (P=0.20): CHIPS primary outcome, birth weight <10th percentile, preeclampsia, preterm delivery, elevated liver enzymes (all P<0.001), platelets <100×109/L (P=0.006), and prolonged hospital stay (P=0.03). The association between severe hypertension and serious maternal complications was seen only in less tight control (P=0.02). Adjustment for preeclampsia (464, 47.3%) did not negate the relationship between severe hypertension and the CHIPS primary outcome (P<0.001), birth weight <10th percentile (P=0.005), delivery at <37 (P<0.001) or <34 weeks (P<0.001), or elevated liver enzymes with symptoms (P=0.02). Severe hypertension is a risk marker for adverse maternal and perinatal outcomes, independent of BP control or preeclampsia co-occurrence. CLINICAL TRIAL REGISTRATION: URL: http://pre-empt.cfri.ca/. Unique identifier: ISRCTN 71416914. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01192412.

Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412). DESIGN: Quantitative and qualitative analysis of questionnaire responses. SETTING: International randomised trial (94 sites, 15 countries). POPULATION/SAMPLE: 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires. METHODS: A questionnaire was administered at ∼6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views. MAIN OUTCOME MEASURES: Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend. RESULTS: Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p≤0.01), and pre-eclampsia (p<0.001). CONCLUSIONS: Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes.

The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial).

UNLABELLED: The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned "less tight" (target diastolic 100 mm Hg) and "tight" (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman-infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, -$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, -$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, -$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412.

Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial.

INTRODUCTION: For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes. MATERIAL AND METHODS: This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model. RESULTS: Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance. CONCLUSIONS: CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy.

The hypertensive disorders of pregnancy (29.3).

Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.