Predictive biomarkers and initial analysis of maternal immune alterations in postpartum preeclampsia reveal an immune-driven pathology.

Introduction: Postpartum preeclampsia (PPPE) is an under-diagnosed condition, developing within 48 hours to 6 weeks following an uncomplicated pregnancy. The etiology of PPPE is still unknown, leaving patients vulnerable and making the identification and treatment of patients requiring postpartum care an unmet need. We aimed to understand the immune contribution to PPPE at the time of diagnosis, as well as uncover the predictive potential of perinatal biomarkers for the early postnatal identification of high-risk patients. Methods: Placentas were collected at delivery from uncomplicated pregnancies (CTL) and PPPE patients for immunohistochemistry analysis. In this initial study, blood samples in PPPE patients were collected at the time of PPPE diagnosis (48h-25 days postpartum; mean 7.4 days) and compared to CTL blood samples taken 24h after delivery. Single-cell transcriptomics, flow cytometry, intracellular cytokine staining, and the circulating levels of inflammatory mediators were evaluated in the blood. Results: Placental CD163+ cells and 1st trimester blood pressures can be valuable non-invasive and predictive biomarkers of PPPE with strong clinical application prospects. Furthermore, changes in immune cell populations, as well as cytokine production by CD14+, CD4+, and CD8+ cells, suggested a dampened response with an exhausted phenotype including decreased IL1ß, IL12, and IFNγ as well as elevated IL10. Discussion: Understanding maternal immune changes at the time of diagnosis and prenatally within the placenta in our sizable cohort will serve as groundwork for pre-clinical and clinical research, as well as guiding clinical practice for example in the development of immune-targeted therapies, and early postnatal identification of patients who would benefit from more thorough follow-ups and risk education in the weeks following an uncomplicated pregnancy.

Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes.

AIMS: Glycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. METHODS: We reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1-5.2 mmol/L, 1 h PG 10.0-10.5 mmol/L, or 2 h PG 8.5-8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. RESULTS: There were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. CONCLUSION: The diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.

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.

Association between proteinuria and placental pathology in preeclampsia: A retrospective study.

INTRODUCTION: Preeclampsia develops due to placental insufficiency and systemic proinflammatory and antiangiogenic mediator release, with ensuing systemic endothelial dysfunction. Nephrotic-range proteinuria appears to be associated with worse pregnancy outcomes. The relationship between differing degrees of proteinuria and the severity of placental alterations has not been studied. METHODS: This is a single-centre retrospective comparison of 150 singleton pregnancies complicated by preeclampsia and varying degrees of proteinuria. Maternal demographic, obstetrical and fetal outcome data were obtained from chart review. The placental histologic evaluations were performed by a placental pathologist blinded to all other clinical information. RESULTS: Preeclamptic women with massive proteinuria had evidence of more severe maternal vascular malperfusion lesions. The severity of the lesions was progressive through mild, moderate and massive proteinuria. Women with massive proteinuria had a higher incidence of renal dysfunction and severe hypertension, and had earlier preterm deliveries compared to preeclamptic women with mild and moderate proteinuria (p < 0.05). CONCLUSION: Preeclampsia with more severe proteinuria is associated with a higher prevalence of placental maternal vascular malperfusion.

Maternal Sleep-Disordered Breathing in Pregnancy and Increased Nocturnal Glucose Levels in Women with Gestational Diabetes Mellitus.

BACKGROUND: Women with hyperglycemia during pregnancy are at high risk for adverse perinatal outcomes. Maternal sleep-disordered breathing (SDB) during pregnancy is common and is a risk factor for gestational diabetes mellitus (GDM). However, the relationship between SDB severity and glucose control is unknown. RESEARCH QUESTION: Is there an association between SDB severity and glucose levels as assessed by continuous glucose monitoring in GDM? STUDY DESIGN AND METHODS: Women with GDM underwent sleep recordings and 72-hour continuous glucose monitoring. Linear mixed models were used to estimate the association of the apnea-hypopnea index (AHI), rapid eye movement (REM)-AHI, and non-REM-AHI with mean glucose levels during nighttime (two periods: 11 pm to 3 am and 3 am to 6 am), daytime (8 am to 9 pm), and 24-hours. Models were adjusted for BMI and antihyperglycemic medications. RESULTS: In 65 participants who were 35 ± 5 (mean ± SD) years of age with BMI of 33 ± 7 kg/m2, 31% were undergoing insulin and/or metformin therapy. A ten-unit increase in AHI was associated with elevated nocturnal glucose levels (11 pm to 3 am: 0.20 mmol/L [95% CI, 0.04-0.40]) with persistent elevations into the morning (8 am: 0.26 mmol/L [95% CI, 0.08-0.4]) when adjusted for BMI and medications. REM-AHI was also associated with higher nocturnal and morning glucose levels, whereas non-REM was not. AHI was not associated with either mean daytime or 24-hour glucose levels. INTERPRETATION: Greater severity of SDB was associated with higher nocturnal and morning glucose levels in women with GDM.

Are blood pressure level and variability related to pregnancy outcome? Analysis of control of hypertension in pregnancy study data.

OBJECTIVE: To examine the relationship between pregnancy outcomes and BP level and variability. DESIGN: Secondary analysis of CHIPS trial data (Control of Hypertension In Pregnancy Study, NCT01192412). SETTING: International. POPULATION OR SAMPLE: Women with chronic or gestational hypertension. METHODS: BP measurement was standardised in outpatient clinics. Adjusted (including for allocated group) mixed effects logistic regression was used to assess relationships between major CHIPS outcomes and both BP level (mean of clinic readings) and visit-to-visit within-participant BP variability (standard deviation and average real variability of absolute successive difference of BP values). BP values 7-28 days prior to outcomes (or birth for perinatal outcomes) were excluded in sensitivity analyses. MAIN OUTCOME MEASURES: Major CHIPS outcomes. RESULTS: Among 961 (97.4%) women, higher BP level was associated with more adverse maternal and perinatal outcomes (usually at p < 0.001) except for serious maternal complications. Among 913 (92.5%) women with at least two post-randomisation outpatient visits, higher BP variability was associated with increased odds of severe hypertension and pre-eclampsia (usually at p < 0.01). Sensitivity analyses suggested reverse causality for these maternal outcomes, but greater diastolic BP variability may have been associated with fewer adverse perinatal outcomes. CONCLUSIONS: Higher BP is an adverse prognostic marker, regardless of target BP. While the association between higher BP variability and severe hypertension and pre-eclampsia may be related to higher BP at diagnosis, our results suggest a possible advantage of BP variability for the fetus, through undefined mechanisms. TWEETABLE ABSTRACT: Higher blood pressure (BP) is associated with more adverse pregnancy outcomes, but higher BP variability may be good for the baby.

Albumin/Creatinine Ratio for the Detection of Significant Proteinuria of Preeclampsia in Hospitalized Hypertensive Women.

OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia. METHODS: A prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records. RESULTS: Of the 87 women who had completed urine collection, 74 (85%) had an initial diagnosis of preeclampsia and 63 (72%) had significant proteinuria confirmed by 24-hour collection. The area under the morning ROC curve was 0.92 (95% CI 0.86-0.98) and the optimal threshold obtained for the ACR was 9 mg/mmol, with a sensitivity and specificity of 84% (95% CI 73-92) and 88% (95% CI 68-97), respectively. CONCLUSION: Our results suggest that an ACR threshold of 9 mg/mmol on a morning urine sample can be used to detect significant proteinuria of preeclampsia in hospitalized hypertensive women.

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.

Blood pressure and burden of hypertension in Cameroon, a microcosm of Africa: a systematic review and meta-analysis of population-based studies.

OBJECTIVE: To estimate national and geography-based variations in blood pressure and burden of hypertension in Cameroon, generally called 'miniature Africa'. METHODS: PubMed, Medline, EMBASE, CINHAL, Web of Science, Popline, Scopus and BDSP were searched through November 2018, for hypertension studies among Cameroonians aged at least 18 years. Hypertension was measured as SBP at least 140 mmHg or DBP at least 90 mmHg. Random-effects meta-analysis was used. RESULTS: Twenty studies involving 46 491 participants met inclusion criteria. Overall hypertension prevalence was 30.9% [95% confidence interval (CI) 27.0-34.8]: 29.6% (24.1-35.1) and 32.1% (27.2-37.1) in 1994-2010 and 2011-2018, respectively. Of hypertensive participants, only 24.4% (18.9-30.0) - 31.6% (21.0-42.3) and 20.8% (14.0-27.7) in 1994-2010 and 2011-2018, respectively - were aware of their status, 15.1% (10.6-19.6) were taking antihypertensive medications and 8.8% (5.7-11.9) - 10.4% (7.5-13.3) and 8.3% (4.4-12.3) in 1994-2010 and 2011-2018, respectively - were controlled. Hypertension prevalence varied by sex: 34.3% (30.0-38.6) for men and 31.3% (26.5-36.1) for women; ethnicity: from 3.3% (0.4-6.2) among Pygmies to 56.6% (49.4-63.8) among Bamileke; urbanity: 25.4% (17.1-33.7) for rural and 31.4% (27.3-35.5) for urban dwellers; agroecological zone: from 35.1% (28.9-41.3) in Tropical highlands to 28% (20.1-35.9) in Guinea-Savannah; and subnational region: from 36.3% (27.8-44.9) in the West to 17.1% (9.9-44.2) in the South. CONCLUSION: Cameroon's hypertension prevalence is high and increasing whereas awareness, treatment and control are low and declining. Emerging patterns call urgently for effective campaigns to raise hypertension awareness alongside strategies for hypertension prevention and BP control.

Distinct inflammatory profile in preeclampsia and postpartum preeclampsia reveal unique mechanisms.

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.

The effect of bromocriptine on left ventricular functional recovery in peripartum cardiomyopathy: insights from the BRO-HF retrospective cohort study.

AIMS: Bromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations. METHODS AND RESULTS: Consecutive women with new-onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid-term (6 months) and long-term (last follow-up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid-term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction < 0.01). At long-term, a similar positive association was found with bromocriptine (9% greater LVEF variation, P interaction < 0.01). In linear regressions adjusted for obstetrical, clinical, echocardiographic, and pharmacological variables, treatment with bromocriptine was associated with a greater improvement in LVEF [ß coefficient (standard error), 14.1 (4.4); P = 0.03]. However, there was no significant association between bromocriptine use and the combined occurrence of all-cause death and heart failure events (hazard ratio, 1.18; 95% confidence interval, 0.15 to 9.31), using univariable Cox regressions based over a cumulative follow-up period of 285 patient-years. CONCLUSIONS: In women newly diagnosed with PPCM, treatment with bromocriptine was independently associated with greater LV functional recovery.

A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods.

Background: Gestational diabetes (GDM) is associated with adverse short- and long-term maternal and fetal outcomes. Observational data support a link between sleep-disordered breathing (SDB) during pregnancy and GDM. However, it is unknown whether treatment of SDB with continuous positive airway pressure (CPAP) improves glucose control in this patient population. In addition, CPAP adherence and feasibility as a treatment option in pregnancy is unknown. This pilot randomized, controlled trial aims to primarily determine the feasibility of CPAP treatment in pregnant women with SDB and GDM. This study is also investigating the effect of SDB treatment on 24-h glucose profiles as an exploratory outcome. Objectives: To describe the study methodology in this ongoing study of pregnant women with GDM and SDB. Patients and Methods: Pregnant women with GDM and SDB defined by apnea-hypopnea index (AHI) ≥10 (Chicago Scoring Criteria) on level 2 polysomnography are randomized to either auto titrating CPAP (experimental group) or a nasal dilator strip (control group) until delivery. The primary outcome, objectively-assessed adherence to CPAP, is measured over the course of the treatment period using device-specific software. Recruitment and retention rates will be calculated to assess the feasibility for planning future trials. Twenty-four hour glucose profiles are measured over a 72-h period using the continuous glucose monitoring (CGM) system, before and after the intervention. Conclusion: The results of this study will be highly informative to determine whether CPAP is a feasible treatment for pregnant women with GDM and SDB, a specialized population at risk for substantial comorbidity. The trial results will ultimately be useful in planning future SDB treatment trials in pregnancy and GDM. The study is registered on clinicaltrials.gov (NCT02245659).

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.

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.

Hypertension Canada's 2018 Guidelines for the Management of Hypertension in Pregnancy.

We present Hypertension Canada's inaugural evidence-based Canadian recommendations for the management of hypertension in pregnancy. Hypertension in pregnancy is common, affecting approximately 7% of pregnancies in Canada, and requires effective management to reduce maternal, fetal, and newborn complications. Because of this importance, these guidelines were developed in partnership with the Society of Obstetricians and Gynaecologists of Canada with the main common objective of improving the management of women with hypertension in pregnancy. Guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children are published separately. In this first Hypertension Canada guidelines for hypertension in pregnancy, 7 recommendations for the management of nonsevere and severe hypertension in pregnancy are presented. For nonsevere hypertension in pregnancy (systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 80-109 mm Hg), we provide guidance for the threshold for initiation of antihypertensive therapy, blood pressure targets, as well as first- and second-line antihypertensive medications. Severe hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) requires urgent antihypertensive therapy to reduce maternal, fetal, and newborn adverse outcomes. The specific evidence and rationale underlying each of these guidelines are discussed.

Long-Acting ß2-Agonists and Risk of Hypertensive Disorders of Pregnancy: A Cohort Study.

BACKGROUND: Maternal asthma has been found to be associated with an increased risk of hypertensive disorders of pregnancy (HDP), that is, gestational hypertension, preeclampsia, and eclampsia. There is limited data, however, regarding the relationship between the use of long-acting beta-agonists (LABAs) during pregnancy and these outcomes. OBJECTIVE: To investigate whether exposure to a LABA in addition to an inhaled corticosteroid increases the risk of HDP or preeclampsia/eclampsia, as compared with nonexposure to LABAs, in pregnant women with asthma. METHODS: A cohort of 8,936 pregnancies in women with asthma who delivered between 1998 and 2010 was reconstructed using Quebec (Canada) health administrative databases. Cox proportional hazard regression models, adjusted for potential confounders, were used for statistical analyses. The primary exposure was LABA use (yes/no) measured on the first day of the 20th week of pregnancy. HDP were identified on the basis of recorded diagnoses and on prescriptions of antihypertensive drugs filled on or after the first day of week 20 of gestation. RESULTS: There were 567 (6.3%) cases of HDP and 256 (2.9%) cases of preeclampsia/eclampsia in the cohort, and the rates of both disorders were similar in women exposed or not exposed to LABAs. LABA use was not associated with increased risks of HDP (adjusted hazard ratio, 0.96; 95% CI, 0.69-1.33) or preeclampsia/eclampsia (adjusted hazard ratio, 0.89; 95% CI, 0.53-1.50). CONCLUSIONS: The results of this study provide evidence suggesting the safety of LABAs for the treatment of asthma in pregnancy, in terms of the risks of HDP and preeclampsia/eclampsia.

Impact of maternal obesity on the incidence of pregnancy complications in France and Canada.

The aim of our study was to compare the impact of maternal obesity on the incidence of medical complications of pregnancy in France and Canada. We performed a prospective comparative cohort study using French data, retrieved from a prospective cohort of singleton deliveries, and Canadian data retrieved from QUARISMA, a cluster-randomized controlled trial conducted in Quebec, both between 2009 and 2011. Outcomes studied included, hypertensive disorders of pregnancy (HDP), venous thromboembolism, stillbirth, caesarean delivery and macrosomia. The impact of obesity across both cohorts was studied using univariate and multivariate logistic regression analyses, adjusting for relevant confounders. The French and Canadian databases included 26,973 and 22,046 deliveries respectively, with obesity rates of 9.1% and 16% respectively (p < 0.001). In both cohorts, obesity was significantly associated with an increased rate of HDP, cesarean delivery, and macrosomia. However, in both cohorts the relationship between increasing body mass index and the incidence of medical complication of pregnancy was the same, regardless the outcome studied. In conclusion, obesity is a risk factor for adverse maternal and fetal outcomes in both cohorts. Similar trends of increased risk were noted in both cohorts even though obesity is more prevalent in Canada.

Atrial fibrillation with a structurally normal heart in pregnancy: An international survey on current practice.

BACKGROUND: Little evidence exists for the optimal management of atrial fibrillation with a structurally normal heart in pregnancy. METHODS: A survey was sent to members of two associations to obtain input on optimal management of atrial fibrillation in pregnancy. The survey presented four cases with respect to (1) baseline investigations; (2) rate versus rhythm control; (3) chemical versus electrical cardioversion; and (4) anticoagulation. RESULTS: Sixty-one responders from 11 countries participated. High agreement was noted for baseline investigations. A quarter (25%) of participants chose elective cardioversion even with a reversible precipitant. Electrical cardioversion was preferred over chemical (p < 0.05). Anticoagulation strategies were heterogeneous except in the presence of a left atrial appendage thrombus. DISCUSSION: This study revealed that there was little consensus in current practice in pregnancy beyond basic investigations. An adaptation of established guidelines to the pregnant population would require a meeting of Cardiologists with input from colleagues in Obstetric Medicine.