Women who develop preeclampsia (PE) are at high risk for cardiovascular disease (CVD). Early identification of women with PE who may benefit the most from early cardiovascular risk screening and interventions remains challenging. Our objective was to assess whether cytokine and immune cell profiles after PE are helpful in distinguishing women at low and high CVD risk at 6-months postpartum. Individuals who developed PE were followed for immune cell phenotyping and plasma cytokine quantification at delivery, at 3-months, and at 6-months postpartum. Lifetime CVD risk was assessed at 6-months postpartum, and the immune cell and cytokine profiles were compared between risk groups at each time point. Among 31 participants, 18 (58.1%) exhibited high CVD-risk profiles at 6-months postpartum. The proportion of circulating NK-cells was significantly lower in high-risk participants at delivery (p = 0.04). At 3-months postpartum, high-risk participants exhibited a lower proportion of FoxP3(+) regulatory T-cells (p = 0.01), a greater proportion of CD8(+) T cells (p = 0.02) and a lower CD4(+):CD8(+) ratio (p = 0.02). There were no differences in immune cell populations at 6-months postpartum. There were no differences in plasma cytokines levels between risk groups at any time point. Subtle differences in immune cell profiles may help distinguish individuals at low and high CVD risk in the early postpartum period and warrants further investigation.

Perturbations to extravillous trophoblast (EVT) cell migration and invasion are associated with the development of placenta‐mediated diseases. Phytochemicals found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to influence cell migration and invasion in models of tumorigenesis and noncancerous, healthy cells, however never in EVT cells. We hypothesized that the phenolic compounds present in V. angustifolium leaf extract promote trophoblast migration and invasion. Using the HTR‐8/SVneo human EVT cell line and Boyden chamber assays, the influence of V. angustifolium leaf extract (0 to 2 × 104 ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined. Cellular proliferation and viability were assessed using immunoreactivity to Ki67 (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V. angustifolium leaf extract increased HTR‐8/SVneo cell migration and invasion (p < .01) and did not affect cell proliferation or viability. Chlorogenic acid was identified as a major phenolic compound of the leaf extract and the most active compound. Evidence from Western blot analysis (n = 3) suggests that the effects of the leaf extract and chlorogenic acid on trophoblast migration and invasion are mediated through an adenosine monophosphate‐activated protein (AMP) kinase‐dependent mechanism. Further investigations examining the potential therapeutic applications of this natural health product extract and its major chemical compounds in the context of placenta‐mediated diseases are warranted.

BackgroundImmunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant.MethodsIn a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses.ResultsRates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM.ConclusionsThis study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series.Clinical Trials RegistrationNCT00553228.

Objective: To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM).Outcomes: Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality.Evidence: Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.Values: The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care.Benefits, Harms, and Costs: Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition.Validation: This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC.Sponsor: The Society of Obstetricians and Gynaecologists of Canada.Recommendations1. Following PPROM at <= 32 weeks' gestation, antibiotics should be administered to women who are not in labour in order to prolong pregnancy and to decrease maternal and neonatal morbidity. (I-A)2. The use of antibiotics should be gestational-age dependent. The evidence for benefit is greater at earlier gestational ages (< 32 weeks). (I-A)[GRAPHICS]3. For women with PPROM at > 32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity can not be proven and/or delivery is not planned. (I-A)4. Antibiotic regimens may consist of an initial parenteral phase followed by an oral phase, or may consist of only an oral phase. (I-A)5. Antibiotics of choice are penicillins or macrolide antibiotics (erythromycin) in parenteral and/or oral forms. (I-A) In patients allergic to penicillin, macrolide antibiotics should be used alone. (III-B)6. The following two regimens may be used (the two regimens were used in the largest PPROM randomized controlled trials that showed a decrease in both maternal and neonatal morbidity): (1) ampicillin 2 g IV every 6 hours and erythromycin 250 mg IV every 6 hours for 48 hours followed by amoxicillin 250 mg orally every 8 hours and erythromycin 333 mg orally every 8 hours for 5 days (I-A); (2) erythromycin 250 mg orally every 6 hours for 10 days (I-A)7. Amoxicillin/clavulanic acid should not be used because of an increased risk of necrotizing enterocolitis in neonates exposed to this antibiotic. Amoxicillin without clavulanic acid is safe. (I-A)8. Women presenting with PPROM should be screened for urinary tract infections, sexually transmitted infections, and group B streptococcus carriage, and treated with appropriate antibiotics if positive. (II-2B)

IVIG, heparin, and ASA can be an option in patients with recurrent pregnancy loss due to MPVFD and CI.

(BJOG. 2016;123:1143–1151) The Control of Hypertension In Pregnancy Study (CHIPS trial) investigated the impact of a target blood pressure (BP) on maternal and perinatal outcomes by randomizing women with gestational or preexisting hypertension to a diastolic BP target of 100 (“less tight” control group) versus 85 mm Hg (“tight” control group). The present study, a secondary analysis of the CHIPS trial data, aimed to compare pregnancy outcomes between women taking methyldopa or labetalol while considering the allocation of these patients to the “less tight” or “tight” control group.

Objective To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension.Design Secondary analysis of CHIPS Trial cohort.Setting International randomised controlled trial (94 sites, 15 countries).Population or sample Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation.Methods Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors.Main outcome measures CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks.Results Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.320.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), preeclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85).Conclusion These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes.

To determine whether the difference in outcomes between ‘less tight’ (target diastolic blood pressure [dBP] of 100 mmHg) versus ‘tight’ control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS.

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, 85 mmHg) or 'less tight' (target diastolic blood pressure, 100 mmHg) who completed questionnaires.Methods: A questionnaire was administered at similar to 6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site coordinator, 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. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd.

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.

Introduction: Discriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity.Methods: Plasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference <10th percentile for gestational age) at sites in Canada, New Zealand and the United Kingdom. When available, placenta tissue underwent histopathological examination for lesions indicating placental dysfunction, blinded to PlGF and clinical outcome. Lesions were evaluated according to pre-specified severity criteria and an overall severity grade was assigned (0-3, absent to severe). Low PlGF (concentration <5th percentile for gestational age) to identify placental FGR (severity grade >= 2) was assessed and compared with routine parameters for fetal assessment. For all cases, the relationship between PlGF and the sampling-to-delivery interval was determined.Results: Low PlGF identified placental FGR with an area under the receiver-operator characteristic curve of 0.96 [95% CI 0.93-0.98], 98.2% [95% CI 90.5-99.9] sensitivity and 75.1% [95% CI 67.6-81.7] specificity. Negative and positive predictive values were 99.2% [95% CI 95.4-99.9] and 58.5% [95% CI 47.9-68.6], respectively. Low PlGF outperformed gestational age, abdominal circumference and umbilical artery resistance index in predicting placental FGR. Very low PlGF (<12 pg/mL) was associated with shorter sampling-to-delivery intervals than normal PlGF (13 vs. 29.5 days, P < 0.0001).Discussion: Low PlGF identifies small fetuses with significant underlying placental pathology and is a promising tool for antenatal discrimination of FGR from fetuses who are constitutionally-small. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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. 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. 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. 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 CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/CHIPS) randomized women with non-severe pregnancy hypertension to a diastolic blood pressure (dBP) target of 100mmHg ['less tight' (LT) control] vs. 85mmHg ['tight' (T) control]. LT was associated with no perinatal benefit, but more severe maternal hypertension. Labetalol was the recommended post-randomization antihypertensive. We aimed to: (1) determine whether the difference in outcomes between LT vs. T control depended on antihypertensive used; and (2) compare pregnancy outcomes, taking into account allocated group, between women taking methyldopa and those taking labetalol, the two most commonly used antihypertensives in CHIPS.Logistic regression was used for comparisons outlined in objectives (1) and (2). Both analyses adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomization.Of 987 women in CHIPS, labetalol (but not methyldopa) was taken by 433/837 women on antihypertensive therapy [186 (LT) vs. 247 (T)] and methyldopa (but not labetalol) by 223/837 [98 (LT) vs. 125 (T)]. Following adjustment: (1) ORs for outcomes in LT vs. T control were similar between antihypertensive groups, but (2) methyldopa use was associated with a reduction in some outcomes (Table). Additional sensitivity analyses had a trivial impact on results.In this secondary analysis of CHIPS data, outcomes for LT vs. T control were not dependent on use of methyldopa or labetalol. The non-randomized comparisons between methyldopa and labetalol are subject to residual confounding, but there is no evidence that women treated with methyldopa (vs. labetalol) had inferior outcomes.L.A. Magee: Research Support Recipient; Commercial Interest: BMGF. P. von Dadelszen: Consultant, Commercial Interest: Alere International. E. Rey: None. S. Ross: None. E. Asztalos: None. K.E. Murphy: None. J. Menzies: None. J. Sanchez: None. J. Singer: None. A. Gafni: None. A. Gruslin: None. M. Helewa: None. E. Hutton: None. S.K. Lee: None. A.G. Logan: None. W. Ganzevoort: None. R. Welch: None. J.G. Thornton: None. J. Moutquin: None.

Placenta-mediated diseases (PMDs) including preeclampsia and fetal growth restriction are often characterized by shallow trophoblast invasion and incomplete spiral artery remodeling leading to impaired placental perfusion. In this context, umbilical artery (UA) Doppler can be used to detect high resistance to flow characteristic of very late-stage placental disease. We propose that evaluation of intraplacental villous artery (IPVA) resistance can provide earlier detection of increased resistance in placental flow. Seventy-five patients were recruited from the Ottawa Hospital. All had scans at 18 to 20, 28 and 34 weeks of gestation. IPVAs arising perpendicular to the chorionic plate in three regions (placental tips 4 cm away from cord insertion and within 1 cm from cord insertion) were sampled at each gestational age for resistance index (RI) and pulsatility index (PI). UA Doppler was also obtained from a free loop of cord. Pregnancy outcomes were collected from a chart review. Data were analyzed using SAS version 9.4 and standard statistic tests (mean±s.d., Student's t-test, mixed-effects modeling). A total of 53 patients completed the study. Of these, 38 had normal pregnancy outcomes (controls) and 15 (cases) developed PMD (preeclampsia, n=8 and low birth weight/intrauterine growth restriction, n=7). Mean birth weight in the study group was 2482.1±518.85 g. At 18 to 20, 28 and 34 weeks gestation, the mean IPVA resistance indices in the control group were 0.86±0.16, 0.81±0.12 and 0.71±0.12 for PI and 0.57±0.07, 0.55±0.06 and 0.49±0.06 for RI, respectively. However, in the cases developing PMDs, the PIs were 1.09±0.17, 0.95±0.21 and 0.78±0.07 and RIs 0.66±0.07, 0.60±0.07 and 0.54±0.04, respectively (P<0.05). UA PI and RI Doppler did not differ between the groups as early as 18 to 20 weeks gestation. Doppler measures of IPVA appear superior to UA in detecting early changes related to PMD. IPVA PI and RI Doppler may be useful in the early identification of patients at risk of PMD.

1 Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, Riverside Campus, University of Ottawa, 1967 Riverside Drive, Ottawa, ON, Canada K1H 7W9 2Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5 3Division of Maternal Fetal Medicine, Departments of Obstetrics and Gynaecology and Cellular Molecular Medicine, University of Ottawa, 501 Smyth Road, Box 804, Ottawa, ON, Canada K1H 8L6 4Chronic Disease Program, Ottawa Hospital Research Institute,The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 5Department of Obstetrics and Gynaecology, Winchester District Memorial Hospital, 566 Louise Street, Winchester, ON, Canada K0C 2K0

The success of pregnancy is dependent on the precise regulation of the immune response within the utero-placental environment. Rats are beginning to be widely used as a model for human immune-related pregnancy complications. However, our knowledge of immune cells and cytokine localization in the rat utero-placental tissue is limited. The current study aimed to localize the immune cell populations, including uterine natural killer (uNK) cells, neutrophils, and macrophages within the rat utero-placental unit at two crucial gestational ages, gestational days 15.5 and 18.5. In addition, we characterized the distribution of the cytokines TNFα, IFNγ, and IL-10 in the utero-placental regions at both the above-mentioned gestational ages. Our study has demonstrated co-localization TNFα and IFNγ with uNK cells in perivascular regions of the rat mesometrial triangle at both gestational ages. Neutrophils and IL-10-positive cells were localized at the maternal-fetal interface and in the spiral artery lumen of the rat mesometrial triangle at both gestational ages. TNFα and IL-10 demonstrated a temporal change in the localization from GD15.5 to GD18.5, which coincides with the leading edge of trophoblast invasion into the mesometrial triangle. The current study furthers our knowledge of the localization of uterine immune cells and relevant cytokines, and provides a base from which to research the function of these immune cells and cytokines during rat pregnancy as a model to study human immune-related pregnancy complications.

Background: Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy.Methods: Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine.Results: Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients.Conclusions: Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety.

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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.