Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

BACKGROUND: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling. METHODS: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed. RESULTS: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07-0.05; P<0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m2; 95% CI, -7.99 to -4.74; P<0.001), end-diastolic volume (-3.87 mL/m2; 95% CI, -6.77 to -0.98; P=0.009), and end-systolic volume (-3.25 mL/m2; 95% CI, 4.87 to -1.63; P<0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P<0.001) and 2.8% (95% CI, 1.4-4.1; P<0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P=0.024) and a reduction in left atrial volumes of -4.33 mL/m2 (95% CI, -5.52 to -3.21; P<0.001) between baseline and follow-up when adjusted for baseline differences in measures. CONCLUSIONS: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04273854.

Microvascular dysfunction in women with a history of hypertensive disorders of pregnancy: A population-based retrospective cohort study.

OBJECTIVE: To evaluate microvascular function in women with previous hypertensive disorders of pregnancy (HDP). DESIGN: Retrospective population-based cohort study. SETTING: Linköping, Sweden. POPULATION: Women aged 50-65 years, participating in the Swedish CArdioPulmonary bioImage Study (SCAPIS) at one site (Linköping) 2016-18, who underwent microcirculatory assessment (N = 1222). METHODS: Forearm skin comprehensive microcirculatory assessment was performed with a PeriFlux PF6000 EPOS (Enhanced Perfusion and Oxygen Saturation) system measuring oxygen saturation and total speed resolved perfusion. Obstetric records were reviewed to identify women with previous HDP. Data on cardiovascular risk factors, comorbidities, medication, lifestyle, anthropometric data, and biochemical analyses were obtained from SCAPIS. The microcirculatory data were compared between women with and without previous HDP. MAIN OUTCOME MEASURES: Skin microcirculatory oxygen saturation and total speed resolved perfusion at baseline and post-ischaemic peak. RESULTS: Women with previous pre-eclampsia displayed impaired post-ischaemic peak oxygen saturation compared with women with normotensive pregnancies (88%, interquartile range [IQR] 84-89% vs 91%, IQR 87-94%, p = 0.001) 6-30 years after pregnancy. The difference remained after multivariable adjustment (ß -2.69, 95% CI -4.93 to -0.45). CONCLUSIONS: The findings reveal microvascular dysfunction at long-term follow up in women with previous pre-eclampsia and strengthen the possible role of endothelial dysfunction as a link to the increased risk of cardiovascular disease in women with HDP.

Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study.

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2-1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5-3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics study may differentiate pre-eclampsia from gestational hypertension.

OBJECTIVE: To investigate the findings of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and serum metabolomics for differentiating pre-eclampsia (PE) from gestational hypertension (GH). METHODS: This prospective study enrolled 176 subjects including a primary cohort with healthy non-pregnant women (HN, n = 35), healthy pregnant women (HP, n = 20), GH (n = 27), and PE (n = 39) and a validation cohort with HP (n = 22), GH (n = 22), and PE (n = 11). T1 signal intensity index (T1SI), apparent diffusion coefficient (ADC) value, and the metabolites on MRS were compared. The differentiating performances of single and combined MRI and MRS parameters for PE were evaluated. Serum liquid chromatography-mass spectrometry (LC-MS) metabolomics was investigated by sparse projection to latent structures discriminant analysis. RESULTS: Increased T1SI, lactate/creatine (Lac/Cr), and glutamine and glutamate (Glx)/Cr and decreased ADC value and myo-inositol (mI)/Cr in basal ganglia were found in PE patients. T1SI, ADC, Lac/Cr, Glx/Cr, and mI/Cr yielded an area under the curves (AUC) of 0.90, 0.80, 0.94, 0.96, and 0.94 in the primary cohort, and of 0.87, 0.81, 0.91, 0.84, and 0.83 in the validation cohort, respectively. A combination of Lac/Cr, Glx/Cr, and mI/Cr yielded the highest AUC of 0.98 in the primary cohort and 0.97 in the validation cohort. Serum metabolomics analysis showed 12 differential metabolites, which are involved in pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism. CONCLUSIONS: MRS is expected to be a noninvasive and effective tool for monitoring GH patients to avoid the development of PE. KEY POINTS: • Increased T1SI and decreased ADC value in the basal ganglia were found in PE patients than in GH patients. • Increased Lac/Cr and Glx/Cr, and decreased mI/Cr in the basal ganglia were found in PE patients than in GH patients. • LC-MS metabolomics showed that the major differential metabolic pathways between PE and GH were pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism.

Experiences of women with hypertensive disorders of pregnancy: a scoping review.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) constitute one of the leading causes of maternal and perinatal mortality worldwide, and are associated with an increased risk of recurrence and future cardiovascular disease. HDP affect women's health condition, mode of birth and timing, length of hospital stay, and relationship with their newborn and family, with future life repercussions. AIMS: To explore the experiences of women with HDP from pregnancy to postpartum, and to identify (a) their perceptions and understanding of HDP, (b) their understanding of future health risks, and (c) the possible interventions by healthcare providers. METHODS: A scoping review was conducted following the Joanna Briggs Institute method and in accordance with the PRISMA-ScR checklist. The following databases were searched from 1990 to 2020 (October): MEDLINE (PubMed), EMBASE, Cochrane Library, CINAHL, PsycINFO, and Google Scholar database. The Critical Appraisal Skills Programme (CASP) checklist was used as a guide for the qualitative analysis. Content analysis and synthesis of findings were conducted using Nvivo12. RESULTS: Of the 1971 articles identified through database searching, 16 articles met the inclusion criteria. After data extraction, content analysis yielded six categories: 'Life-threatening disorder', 'Coping with HDP', 'Concerns for baby and challenges of motherhood', 'Fear of recurrence and health problems', 'Necessity of social and spiritual support', and 'Positive and negative experiences in the healthcare context'. Women faced complex difficulties from the long treatment process while transitioning to motherhood. CONCLUSION: Our findings revealed the perceptions and understanding of women regarding HDP as a life-threatening disorder to both mothers and their babies which mothers need to cope with. Recovery of physical condition and the long-term psychological effects of HDP on women should be given attention by mothers and HCP to reduce future health risks. Importantly, a lifelong follow-up system is recommended for women with HDP.

Association of Maternal Hypertensive Disorders During Pregnancy With Severe Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis was performed to examine the association between maternal hypertension during pregnancy (HDP) and neonatal bronchopulmonary dysplasia (BPD). METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library, and the KoreaMed database for relevant studies. We used the Newcastle-Ottawa Scale for quality assessment of all included studies. The meta-analysis was performed using Comprehensive Meta-Analysis software (version 3.3). RESULTS: We included 35 studies that fulfilled the inclusion criteria; the total number of infants evaluated came to 97,399 through review process. Maternal HDP was not significantly associated with any definition of BPD, i.e., oxygen dependency at 36 weeks of gestation (odds ratio [OR], 1.162; 95% confidence interval [CI], 0.991-1.362; P = 0.064) in pooled analysis of 29 studies or oxygen dependency at 28 days of age (OR, 1.084; 95% CI, 0.660-1.780; P = 0.751) in pooled analysis of 8 studies. Maternal HDP was significantly associated only with severe BPD (OR, 2.341; 95% CI, 1.726-3.174; P < 0.001). BPD was not associated with HDP in the overall analysis (OR, 1.131; 95% CI, 0.977-1.309; P = 0.100) or subgroup analysis according to the definition of HDP. CONCLUSION: Maternal HDP was not associated with neonatal BPD defined by the duration of oxygen dependency (at either 36 weeks of gestation or 28 days of life) but was associated with severe BPD.

Adverse pregnancy and perinatal outcomes in Latin America and the Caribbean: systematic review and meta-analysis.

Objective: To estimate the point prevalence and likely ranges of pregnancy-induced hypertension, pre-eclampsia, gestational diabetes, low birth weight and preterm delivery in Latin America and the Caribbean, and evaluate the heterogeneity of the estimates. Methods: We conducted a systematic review and meta-analysis of observational studies reporting the prevalence of maternal and perinatal adverse outcomes in populations in Latin American and the Caribbean published between 2000 and 2019 in English, Spanish, or Portuguese. We searched PubMed, Embase, and LILACS. We estimated the point prevalence and evaluated overall heterogeneity and, in sub-group analyses, heterogeneity by study design and level of bias. Results: Of 1087 records retrieved, 50 articles were included in the review: two on hypertensive disorders of pregnancy, 14 on pre-eclampsia, six on gestational diabetes, nine on low birth weight and 19 on preterm birth. No meta-analysis for hypertensive disorders of pregnancy could be done because of the small number of studies. Point prevalence estimates and 95% confidence intervals (CIs) for pre-eclampsia, gestational diabetes, low birth weight, and preterm birth were: 6.6% (95% CI: 4.9%, 8.6%), 8.5% (95% CI: 3.9%, 14.7%), 8.5% (95% CI: 7.2%, 9.8%), and 10.0% (95% CI: 8.0%, 12.0%), respectively. We observed substantial heterogeneity overall and by study design. No major differences in estimates were observed by level of bias. Conclusions: The results of this study provide updated estimates of some of the most prevalent adverse pregnancy and perinatal outcomes in Latin America and the Caribbean. They highlight that important heterogeneity exists in prevalence estimates, which may reflect the diversity of populations in the region.

Impact of the 2017 ACC/AHA Guideline for High Blood Pressure on Evaluating Gestational Hypertension-Associated Risks for Newborns and Mothers.

RATIONALE: In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) released a new hypertension guideline for nonpregnant adults, using lower blood pressure values to identify hypertension. However, the impact of this new guideline on the diagnosis of gestational hypertension and the associated maternal and neonatal risks are unknown. OBJECTIVE: To estimate the impact of adopting the 2017 ACC/AHA guideline on detecting gestational blood pressure elevations and the relationship with maternal and neonatal risk in the perinatal period using a retrospective cohort design. METHODS AND RESULTS: This study included 16 345 women from China. Systolic and diastolic blood pressures of each woman were measured at up to 22 prenatal care visits across different stages of pregnancy. Logistic and linear regressions were used to estimate associations of blood pressure categories with the risk of preterm delivery, early-term delivery, and small for gestational age, and indicators of maternal liver, renal, and coagulation functions during pregnancy. We identified 4100 (25.1%) women with gestational hypertension using the 2017 ACC/AHA guideline, compared with 4.2% using the former definition. Gestational hypertension, but not elevated blood pressure (subclinical blood pressure elevation), was significantly associated with altered indicators of liver, renal, and coagulation functions during pregnancy for mothers and increased risk of adverse birth outcomes for newborns; adjusted odds ratios (95% CIs) for gestational hypertension stage 2 were 2.23 (1.18-4.24) for preterm delivery, 2.05 (1.67-2.53) for early-term delivery, and 1.43 (1.13-1.81) for small for gestational age. CONCLUSIONS: Adopting the 2017 ACC/AHA guideline would result in a substantial increase in the prevalence of gestational hypertension; subclinical blood pressure elevations during late pregnancy were not associated with increased maternal and neonatal risk in this cohort. Therefore, the 2017 ACC/AHA guideline may improve the detection of high blood pressure during pregnancy and the efforts to reduce maternal and neonatal risk. Replications in other populations are required.

Impact of an Educational Pamphlet on Knowledge About Health Risks After Hypertensive Disorders of Pregnancy: A Randomized Trial.

OBJECTIVE: To evaluate patients' knowledge, risk perception, and anxiety about future health risks after an episode of hypertensive disorder of pregnancy (HDP), as well as their satisfaction with an educational pamphlet. METHODS: From January 2016 to June 2017, participants were randomly assigned to one of 2 groups and asked to complete questionnaire #1 (demographics, knowledge, risk perception, anxiety, and satisfaction) after receiving medical counselling at the HDP postpartum clinic. Participants in the intervention group then received the educational pamphlet. One month later, both groups completed the questionnaire again (questionnaire #2). The primary outcome of this study was improvement in the global knowledge score at 1 month, reflecting improved understanding of the health risks of HDP. Secondary outcomes included retention of information, risk perception, satisfaction, and anxiety level. RESULTS: Of 137 eligible women, 57 were randomly assigned to the intervention group and 56, to the control group. Participants in both groups had similar baseline characteristics. Thirteen percent of participants did not complete questionnaire #2. The knowledge score was higher in the intervention group than the control group at 1 month, (88.2%; 95% confidence interval [CI] 26.37-28.32 and 71.3%; 95% CI 20.78-23.45, respectively [P <0.0001]). No difference was seen in anxiety level between the groups (4.0 ± 1.00 vs. 3.8 ± 0.92; P = 0.6746). The intervention group was highly satisfied with the medical counselling they received (5.5 ± 0.84 out 6) and with the pamphlet (5.6 ± 0.66 out 6). CONCLUSION: The educational pamphlet increased women's knowledge about future health risks of HDP without increasing anxiety and it may be helpful in promoting lifestyle changes necessary to modify these risks.

Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records: A CALIBER Study.

BACKGROUND: The associations between pregnancy hypertensive disorders and common cardiovascular disorders have not been investigated at scale in a contemporaneous population. We aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders. METHODS: We used linked electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women, mean age at delivery 28 years, with nearly 1.9 million completed pregnancies. We used multivariable Cox models to determine the associations between hypertensive disorders of pregnancy, and preeclampsia alone (term and preterm), with 12 cardiovascular disorders in addition to chronic hypertension. We estimated the cumulative incidence of a composite end point of any cardiovascular disorder according to preeclampsia exposure. RESULTS: During the 20-year study period, 18 624 incident cardiovascular disorders were observed, 65% of which had occurred in women under 40 years. Compared to women without hypertension in pregnancy, women who had 1 or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% confidence interval 1.53-2.35) for any stroke, 1.67 (1.54-1.81) for cardiac atherosclerotic events, 1.82 (1.34-2.46) for peripheral events, 2.13 (1.64-2.76) for heart failure, 1.73 (1.38-2.16) for atrial fibrillation, 2.12 (1.49-2.99) for cardiovascular deaths, and 4.47 (4.32-4.62) for chronic hypertension. Differences in cumulative incidence curves, according to preeclampsia status, were apparent within 1 year of the first index pregnancy. Similar patterns of association were observed for hypertensive disorders of pregnancy, while preterm preeclampsia conferred slightly further elevated risks. CONCLUSIONS: Hypertensive disorders of pregnancy, including preeclampsia, have a similar pattern of increased risk across all 12 cardiovascular disorders and chronic hypertension, and the impact was evident soon after pregnancy. Hypertensive disorders of pregnancy should be considered as a natural screening tool for cardiovascular events, enabling cardiovascular risk prevention through national initiatives.

A risk factor-based predictive model for new-onset hypertension during pregnancy in Chinese Han women.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is one of the leading causes of maternal and neonatal mortality, increasing the long-term incidence of cardiovascular diseases. Preeclampsia and gestational hypertension are the major components of HDP. The aim of our study is to establish a prediction model for pregnant women with new-onset hypertension during pregnancy (increased blood pressure after gestational age > 20 weeks), thus to guide the clinical prediction and treatment of de novo hypertension. METHODS: A total of 117 pregnant women with de novo hypertension who were admitted to our hospital's obstetrics department were selected as the case group and 199 healthy pregnant women were selected as the control group from January 2017 to June 2018. Maternal clinical parameters such as age, family history and the biomarkers such as homocysteine, cystatin C, uric acid, total bile acid and glomerular filtration rate were collected at a mean gestational age in 16 to 20 weeks. The prediction model was established by logistic regression. RESULTS: Eleven indicators have statistically significant difference between two groups (P < 0.05). These 11 factors were substituted into the logistic regression equation and 7 independent predictors were obtained. The equation expressed including 7 factors. The calculated area under the curve was 0.884(95% confidence interval: 0.848-0.921), the sensitivity and specificity were 88.0 and 75.0%. A scoring system was established to classify pregnant women with scores ≤15.5 as low-risk pregnancy group and those with scores > 15.5 as high-risk pregnancy group. CONCLUSIONS: Our regression equation provides a feasible and reliable means of predicting de novo hypertension after pregnancy. Risk stratification of new-onset hypertension was performed to early treatment interventions in high-risk populations.

The WHO Safe Childbirth Checklist implementation: impact on the prescription of magnesium sulphate through a one-year longitudinal study.

BACKGROUND: Preeclampsia is a relatively frequent condition during pregnancy and childbirth. The administration of magnesium sulphate as a prophylactic and treatment measure is an evidence-based practice for eclampsia; however, it is not consistently used, compromising the health of pregnant women. This study aimed to assess compliance with recommendations of the International Society for the Study of Hypertension in Pregnancy (ISSHP) for the use of MgSO4 in pregnant women with preeclampsia, before and after the implementation of the World Health Organization Safe Childbirth Checklist (SCC). METHODS: This quasi-experimental study was conducted between July 2015 and July 2016 at a third-level maternity hospital in northeastern Brazil, where the SCC was implemented. Compliance (underuse and overuse of MgSO4) was assessed in biweekly samples of 30 deliveries assessed 6 months before and 6 months after SCC implementation, using indicators based on international guidelines. A total of 720 deliveries were assessed over 1 year using an ad hoc application for reviewing medical records. Aggregated adequate use was estimated for the study period, and the time series measurements were compared to a control chart to assess change. RESULTS: The incidence of preeclampsia was 39.9% (287/720). Among these, 64.8% (186/287) had severe signs or symptoms and needed MgSO4. Underuse (no prescription when needed) of MgSO4 was observed in 74.7% (139/186) of women who needed the drug. Considering all women, non-compliance with the prescription protocol (underuse and overuse) was 20.0% (144/720). After introducing the SCC, the use of MgSO4 in women with preeclampsia with severe features increased from 19.1 to 34.2% (p = 0.025). Longitudinal analysis showed a significant (p < 0.05) ascending curve of adequate use of MgSO4 after the SCC was implemented. CONCLUSIONS: Compliance with recommendations for the use of MgSO4 in preeclampsia was low, but improved after implementation of the SCC. Interventions to improve compliance based on diagnosis and treatment reminders may help in the implementation of this good practice.

Midwives', Obstetricians', and Recently Delivered Mothers' Perceptions of Remote Monitoring for Prenatal Care: Retrospective Survey.

BACKGROUND: The Pregnancy Remote Monitoring (PREMOM) study enrolled pregnant women at increased risk of developing hypertensive disorders of pregnancy and investigated the effect of remote monitoring in addition to their prenatal follow-up. OBJECTIVE: The objective of this study was to investigate the perceptions and experiences of remote monitoring among mothers, midwives, and obstetricians who participated in the PREMOM study. METHODS: We developed specific questionnaires for the mothers, midwives, and obstetricians addressing 5 domains: (1) prior knowledge and experience of remote monitoring, (2) reactions to abnormal values, (3) privacy, (4) quality and patient safety, and (5) financial aspects. We also questioned the health care providers about which issues they considered important when implementing remote monitoring. We used a 5-point Likert scale to provide objective scores. It was possible to add free-text feedback at every question. RESULTS: A total of 91 participants completed the questionnaires. The mothers, midwives, and obstetricians reported positive experiences and perceptions of remote monitoring, although most of them had no or little prior experience with this technology. They supported a further rollout of remote monitoring in Belgium. Nearly three-quarters of the mothers (34/47, 72%) did not report any problems with taking the measurements at the required times. Almost half of the mothers (19/47, 40%) wanted to be contacted within 3 to 12 hours after abnormal measurement values, preferably by telephone. CONCLUSIONS: Although most of midwives and obstetricians had no or very little experience with remote monitoring before enrolling in the PREMOM study, they reported, based on their one-year experience, that remote monitoring was an important component in the follow-up of high-risk pregnancies and would recommend it to their colleagues and pregnant patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03246737; https://clinicaltrials.gov/ct2/show/NCT03246737 (Archived by WebCite at http://www.webcitation.org/76KVnHSYY).

[Effects of human leucocyte antigen-G expression on invasion and proliferation of chorionic trophoblastic cell line JEG-3].

Objective: To investigate the effects of human leukocyte-associated antigen-G (HLA-G) expression in silencing trophoblast cell line JEG-3 under normal and hypoxic conditions on invasion and proliferation of JEG-3 cells. Methods: Inhibition of HLA-G expression in JEG-3 cells by transfection of small interfering RNA (siRNA),the transfected JEG-3 cells were divided into 4 groups: normoxia control group, hypoxia control group, normoxia inhibition group and hypoxia inhibition group. The levels of HLA-G mRNA and protein in 4 groups of cells were detected by real-time quantitive PCR and western blot. The proliferation activity and invasion ability of 4 groups of cells were determined by methylthiazolyl tetrazolium (MTT) assay and invasion assay. Results: (1) Real-time quantitive PCR technology showed: the level of HLA-G mRNA in the hypoxic inhibition group (0.220±0.050) was significantly different (P<0.05), when compared with that in the hypoxic control group (0.630±0.030) and normoxic inhibition group (0.400±0.020). (2) Western blot analysis showed: the expression level of HLA-G protein in the hypoxic inhibition group was 0.260±0.010, statistically different from that in the hypoxic control group (0.850±0.100) and the normoxic inhibition group (0.560±0.020; P<0.05).(3) MTT showed: proliferative activity of JEG-3 cells in the normoxic inhibition group was 0.490±0.070, the ability of cell proliferation was reduced. When compared with that in the normoxic control group (0.850±0.050), the differences was statistically significant (P<0.05). The proliferative activity of JEG-3 cells in the hypoxic inhibition group (0.330±0.070) was lower than that in the normoxic inhibition group (0.490±0.070), and there was a significant difference (P<0.05). (4) Invasion assay showed: compared with the normoxic control group (98±7), the invasive ability of JEG-3 cells in the normoxic inhibition group (73±7) was weakened, and the difference was statistically significant (P<0.05). The number of transmembrane cells (52±11) of JEG-3 cells in the hypoxic inhibition group was lower than that in the hypoxic control group (72±7), and the difference was statistically significant (P<0.05). Compared with the normoxic inhibition group, the invasion ability of JEG-3 cells in the hypoxic inhibition group decreased, and the difference was statistically significant (P<0.05). Conclusion: Under hypoxia, using siRNA technology to down-regulate the expression of HLA-G may affect the proliferation and invasion ability of trophoblast cells, which may be involved in the occurrence of hypertensive disorder of pregnancy.

PREGNANCY OUTCOME IN GESTATIONAL DIABETES COMPARED TO BODY MASS INDEX.

Gestational diabetes involves disorder of glucose metabolism first diagnosed in pregnancy. Obese women undoubtedly have more often complications in reproductive age, such as fertility difficulties, spontaneous and recurrent miscarriages, premature births, and various obstetric and surgical complications related to the course of pregnancy, delivery and puerperium. Children of obese pregnant women are more likely to develop obesity in childhood and adulthood. We analyzed the outcome of 51 pregnancies in obese pregnant women and 50 pregnant women with normal body mass index. All women in both groups were diagnosed with gestational diabetes by the IADPSG criteria. We analyzed gestational age at delivery and mode of delivery, gestational weight gain, presence of concomitant diagnosis of gestational or chronic hypertension, difference in birth weight, and prevalence of hypertrophic newborns. There was no significant difference in gestational age at pregnancy termination and in the mode of delivery. There was a significant difference in gestational weight gain, number of pregnant women with hypertension, neonatal birth weight and number of hypertrophic children. Based on the data presented, we conclude that obesity is an unfavorable factor for pregnancy outcome. It also influences birth weight and fetal hypertrophy, as well as gestational weight gain.

Phosphodiesterase Inhibition in the Treatment of Preeclampsia: What Is New?

PURPOSE OF REVIEW: The present study intends to review the possibility of using phosphodiesterase inhibitors as a treatment option for preeclampsia, addressing potential risks and benefits. RECENT FINDINGS: Preeclampsia is the most common hypertensive disorder of pregnancy, often responsible for severe maternal and fetal complications, which can lead to early pregnancy termination and death. Despite the numerous studies, its pathophysiology is still unclear, although it seems to involve a multiplicity of complex factors related to angiogenesis, ineffective vasodilation, oxidative stress, inflammatory cytokines, and endothelial dysfunction. It has been hypothetically suggested that the use of phosphodiesterase inhibitors is capable of improving placental and fetal perfusion, contributing to gestational scenario, by decreasing the symptomatology and severity of this syndrome. In this literature review, it has been found that most of the studies were conducted in animal models, and there is still lack of evidence supporting its use in clinical practice. Research in human indicates conflicting findings; randomized controlled trials were scarce and did not demonstrate any benefit in morbidity or mortality. Data regarding to pathophysiological and interventional research are described and commented in this review. The use of phosphodiesterase inhibitors in the treatment of preeclampsia is controversial and should not be encouraged taking into account recent data.

Delayed Lactogenesis II and potential utility of antenatal milk expression in women developing late-onset preeclampsia: a case series.

BACKGROUND: Preeclampsia is a multi-system, hypertensive disorder of pregnancy that increases a woman's risk of later-life cardiovascular disease. Breastfeeding may counteract the negative cardiovascular sequela associated with preeclampsia; however, women who develop preeclampsia may be at-risk for suboptimal breastfeeding rates. In this case series, we present three cases of late-onset preeclampsia and one case of severe gestational hypertension that illustrate a potential association between hypertensive disorders of pregnancy and suboptimal breastfeeding outcomes, including delayed onset of lactogenesis II and in-hospital formula supplementation. CASE PRESENTATION: All cases were drawn from an ongoing pilot randomized controlled trial investigating the impact of antenatal milk expression versus an education control on breastfeeding outcomes. All study participants were healthy nulliparous women recruited at 34-366/7 gestational weeks from a hospital-based midwife practice. The variability in clinical presentation among the four cases suggests that any effect of hypertensive disorders on breastfeeding outcomes is likely multifactorial in nature, and may include both primary (e.g., preeclampsia disease course itself) and secondary (e.g., magnesium sulfate therapy, delayed at-breast feeding due to maternal-infant separation) etiologies. We further describe the use of antenatal milk expression (AME), or milk expression and storage beginning around 37 weeks of gestation, as a potential intervention to mitigate suboptimal breastfeeding outcomes in women at risk for preeclampsia and other hypertensive disorders of pregnancy. CONCLUSIONS: Additional research is needed to address incidence, etiology, and interventions, including AME, for breastfeeding issues among a larger sample of women who develop hypertensive disorders of pregnancy.

[High risk factors analysis of stillbirth].

Objective: To explore the high risk factors of stillbirth. Methods: 176 cases of stillbirth were collected in the Obstetrics and Gynecology Hospital of Fudan University from January 1(st), 2010 to December 31(st), 2016. All cases were analyzed retrospectively, including general profile, high risk factors of stillbirth in different years and pregnancy periods. Results: (1) The incidence of stillbirth was 0.178%(176/98 785). Stillbirth occured mostly at 28-28(+6) gestational weeks (10.8%,19/176), and the second peak was 29-29(+6) weeks(10.2%,18/176), while the third common period was 37-37(+6) weeks (9.1%,16/176). After 39 weeks, it maintained at a low level. (2) The top 5 high risk factors of stillbirth were infection (18.2%,32/176), unexplained (13.6%,24/176), hypertention disorders in pregnancy (13.1%, 23/176), umbilical cord torsion (12.5%, 22/176) and fetal malformations (10.2%, 18/176). (3) From 2010 to 2012, the top 3 high risk factors were unexplained, the umbilical cord torsion and infection, while hypertention in pregnancy, infection and fetal malformation became the top 3 high risk factors after 2013. (4) Early stillbirth (20-27(+6) weeks) accounted for 21.6%(38/176); and unexplained (47.4%, 18/38), fetal edema (13.2%, 5/38),infection (13.2%, 5/38), umbilical cord torsion (5.3%, 2/38) were the top 4 high risk factors. Late stillbirth (≥28 weeks) accounted for 78.4%(138/176), with infection (19.6%,27/138), hypertention in pregnancy (15.9%,22/138), umbilical cord torsion (14.5%,20/138) and fetal malformation(12.3%,17/138)being the top 4 high risk factors. Conclusions: More attention should be paid to maternal complications, especially infection and hypertension in pregnancy. Antenatal fetal monitoring, timely termination of pregnancy, standard management of stillbirth and looking for the causes may help reduce the incidence of stillbirth.

[Effect of blood pressure control level on perinatal outcomes in women with mild-moderate gestational hypertension].

Objective: To investigate the effect of blood pressure (BP) control level on perinatal outcomes in women with mild-moderate gestational hypertension (GHp). Methods: Totally, 344 women diagnosed initially as mild-moderate GHp who delivered in Peking University Third Hospital from January 2012 to December 2016 were recruited. They were divided into four groups according to the stabilized level of BP during pregnancy. (1) Group A: BP<130/80 mmHg (1 mmHg=0.133 kPa) ; (2) Group B: BP (130-139) / (80-89) mmHg; (3) Group C: BP (140-149) / (90-99) mmHg; (4) Group D: BP (150-159) / (100-109) mmHg. The clinical profile and incidence of severe GHp, pre-eclampsia with proteinuria (PE+Upro), severe pre-eclampsia (sPE), small-for-gestational age (SGA) were compared among the four groups. Student t-test was preformed to normal distributive data and Kruskal-Wallis test was used to non-normally distributed variables. Chi-square test was used in count data. Logistic regression analysis was adopted for multiple-factor analysis. Results: (1) The incidence of severe GHp in group A was lower than group B (P<0.05). The incidences of severe GHp and sPE in the group B was lower than those in group C (P<0.05). While there was no difference in the incidence of PE+Upro and SGA among the four groups (P>0.05). And the incidence of severe GHp in group D had no difference with group A, B, C (P>0.05). (2) In the 48 patients who used medications to control BP, the occurence of severe GHp in those whose initial BP was (140-149) / (90-99) mmHg was lower than those of ≥160/110 mmHg (P<0.05). But the incidence of severe GHp had no significant difference between patients whose initial BP was (140-149) / (90-99) mmHg and patients whose initial BP was (150-159) / (100-109) mmHg (P>0.05). The initial BP level had no impact on the incidence of PE+Upro, sPE and SGA (P>0.05). (3) Multivariate logistic regression analysis showed that the BP level before using medications (OR=3.566, 95%CI: 1.080-11.771, P=0.037) and the BP level maintained (OR=4.787, 95%CI: 1.115-20.551, P=0.035) were independent factor that affected the incidence of severe GHp. Edema (OR=2.651, 95% CI: 1.628-4.316 P=0.000), fetal growth restriction (FGR; OR=1.103, 95% CI: 1.427-5.914, P=0.002) and the onset gestational age of GHp (OR=0.755, 95%CI: 0.578-0.985, P=0.038) were independent factors that affected the incidence of PE+Upro. The tendency of FGR (OR=17.787, 95%CI: 1.833-40.396 P=0.000), history of PE (OR=5.294, 95%CI: 1.086-25.800, P=0.039) and the BP level during pregnancy (OR=2.109, 95%CI: 1.274-3.491, P=0.004) were independent factors affecting the incidence of sPE. FGR tendency was independent factor affecting the incidence of SGA (OR=25.622, 95%CI: 2.596-252.864, P=0.005). Conclusion: A satisfied control of BP is helpful to reduce severe GHp and sPE, but the incidence of SGA does not affected.