Integrating evidence and causal mapping of factors that influence medication decision-making by pregnant women at risk of hypertensive disorder: protocol for a scoping review.

INTRODUCTION: In 2018, the American College of Obstetricians and Gynecologists recommended low-dose aspirin to prevent the onset of pre-eclampsia among women who were at high risk. Factors influencing women's acceptance of this recommendation span multiple sectors and levels. Understanding how these factors interact will help stakeholders design effective population-level intervention strategies. Our study aims to identify and map relationships among factors influencing the medication decisions of pregnant women at risk of hypertensive disorders. METHODS AND ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines will be followed for this review. A research librarian developed a comprehensive search strategy to retrieve published and unpublished English studies after 1 January 1980, involving factors that influence pregnant women's uptake and adherence to medication for gestational hypertensive disorders. This literature includes perceptions, patterns, acceptance, refusal, tendencies, probability and service utilisation. We will search PubMed, Embase, Web of Science and CINAHL. Reference lists of the selected papers will be searched manually to identify more relevant studies. A two-stage independent screening, consisting of title and abstract screening, followed by full-text screening, will be conducted by two independent reviewers to identify eligible articles. Extracted data will be recorded in a customised variable extraction form and input into a Microsoft Access database. The PRISMA-ScR will be used to guide the presentation of the results, which will be presented in a table and causal map to demonstrate the relationships between extracted variables and medication uptake and adherence. A conceptual simulation model will be formulated to validate the logic of the relationships between variables and identify knowledge gaps. Lastly, experts and stakeholders will be invited to critique and comment on the results. ETHICS AND DISSEMINATION: This study does not require ethical approval. The full review results will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication.

Maternal-neonatal events resulting from medications for preventing hypertensive disorders in high-risk pregnant women: A systematic review and network meta-analysis.

BACKGROUND: There have been few studies reporting on maternal and neonatal events in high-risk pregnant women receiving medications for preventing hypertensive disorders of pregnancy (HDP). OBJECTIVE: To identify placental abruption, postpartum hemorrhage, neonatal intraventricular hemorrhage, and neonates with small for gestational age (SGA) or growth restriction resulting from medications for preventing HDP in high-risk pregnant women using a network meta-analysis. SEARCH STRATEGY: All randomized controlled trials comparing the most commonly used medications (antiplatelet agents, anticoagulants, antioxidants, nitric oxide, and calcium) for preventing HDP in high-risk pregnant women were searched from the Cochrane Pregnancy and Childbirth's Specialized Register of Controlled Trials until July 31, 2020, without language restriction. SELECTION CRITERIA: Two of the authors independently selected the eligible trials. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the methodological quality of the included trials. Pairwise and network meta-analyses were used to determine comparative risk ratios and 95% confidence intervals. MAIN RESULTS: The 51 included trials involved 69 669 pregnant women. Compared with placebo/no treatment, antioxidants slightly reduced placental abruption with high-certainty evidence. Antiplatelet agents probably reduced SGA with low-certainty evidence and slightly increased neonatal intraventricular hemorrhage with moderate-certainty evidence. CONCLUSION: Antiplatelet agents probably reduce SGA, but neonatal intraventricular hemorrhage should be monitored. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018096276.

Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women. METHODS: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI). RESULTS: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved. CONCLUSION: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.

The effect of a neonatal sleep intervention on maternal postpartum hypertension: a randomized trial.

BACKGROUND: In nonpregnant adults, poor sleep is associated with higher blood pressure. Poor sleep is common in the postpartum period and is often attributed to infant caretaking needs. However, its effects on cardiovascular health in individuals with a hypertensive disorder of pregnancy are unknown. OBJECTIVE: This study aimed to determine the effect of a neonatal sleep intervention on maternal postpartum blood pressure in individuals with a hypertensive disorder of pregnancy. STUDY DESIGN: In this single-institution pilot randomized controlled trial from July 2021 to March 2022, 110 individuals with a hypertensive disorder of pregnancy were randomized to receive a neonatal sleep intervention (SNOO responsive bassinet) plus usual care of safe sleep education (n=54) or usual care alone (n=56). Remote follow-up visits were conducted at 1 week, 6 weeks, and 4 months after delivery and involved blood pressure and weights, sleep and mood questionnaires, and self-reported infant and maternal sleep logs. Based on institutional data, the sample size had 80% power to detect a 4.5-mm Hg difference in the primary outcome of mean arterial pressure at 6 weeks after delivery. RESULTS: Baseline characteristics were similar between the arms. At 1 week after delivery, the intervention arm had lower mean arterial pressure and less antihypertensive medication use than the control arm (99±10 vs 103±7 mm Hg [P=.04] and 23% vs 35% [P=.15], respectively). At 6 weeks after delivery, mean arterial pressure was similar between arms (93±8 vs 94±8 mm Hg; P=.54), but there was a lower rate of antihypertensive use in the intervention arm (15% vs 26%; P=.19). Scores from maternal sleep and mood questionnaires at 6 weeks after delivery and self-reported infant and maternal sleep duration at 6 weeks and 4 months after delivery were similar between arms (P>.05). CONCLUSION: The SNOO responsive bassinet as a neonatal sleep intervention did not result in improved mean arterial pressure at 6 weeks after delivery after hypertensive disorders of pregnancy.

Prepregnancy Healthy Lifestyle and Adverse Pregnancy Outcomes.

OBJECTIVE: To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous physical activity, healthy eating [top 40% of Dietary Approaches to Stop Hypertension score], no or low-to-moderate alcohol intake [less than 15 g/d], and use of multivitamins) with risk of adverse pregnancy outcomes. METHODS: We conducted a secondary analysis of prospectively collected data for women without chronic diseases who are participating in an ongoing cohort in the United States (the NHSII [Nurses' Health Study II]). Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2-4 years from 1991 to 2009 with validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of adverse pregnancy outcomes that included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, or low birth weight was assessed. RESULTS: Overall, 15,509 women with 27,135 pregnancies were included. The mean maternal age was 35.1±4.2 years. Approximately one in three pregnancies (n=9,702, 35.8%) was complicated by one or more adverse pregnancy outcomes. The combination of six low-risk factors was inversely associated with risk of adverse pregnancy outcomes in a dose-dependent manner ( P for trend <.001). Compared with women who had zero or one healthy lifestyle factor, those with six had a 37% lower risk of adverse pregnancy outcomes (relative risk 0.63, 95% CI 0.55-0.72), driven primarily by lower risks of gestational diabetes, gestational hypertension, and low birth weight. All prepregnancy healthy lifestyle factors, except avoiding harmful alcohol consumption and regular physical activity, were independently associated with lower risk of adverse pregnancy outcomes after mutual adjustment for each other. Healthy BMI, high-quality diet, and multivitamin supplementation showed the strongest inverse associations with adverse pregnancy outcomes. If the observed relationships were causal, 19% of adverse pregnancy outcomes could have been prevented by the adoption of all six healthy lifestyle factors (population attributable risk 19%, 95% CI 13-26%). CONCLUSION: Prepregnancy healthy lifestyle is associated with a substantially lower risk of adverse pregnancy outcomes and could be an effective intervention for the prevention of adverse pregnancy outcomes.

Barriers and Facilitators to Cardiovascular Disease Prevention Following Hypertensive Disorders of Pregnancy in Primary Care: Cross-Sectional Surveys.

Women with a history of hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease (CVD). Guidelines recommend that women diagnosed with HDP should be advised of their increased CVD risk, have regular blood pressure monitoring by their general practitioner (GP), and adopt healthy lifestyle behaviours. However, within Australia, the current practice in primary health care is unknown. The aim of this study was to describe current practices, barriers, and facilitators to the provision of CVD preventative services for women after HDP in the primary care setting and to identify potential strategies to support GPs in providing recommended care. Separate cross-sectional online surveys were undertaken with 35 GPs and 105 women with a history of HDP. Surveys included both closed- and open-ended questions. Closed-ended questions were analysed using basic descriptive statistics, and open-ended questions were themed and tallied. The survey of GPs revealed that GPs are more likely to assess traditional CVD risk markers than lifestyle risk factors or HDP history. GPs identified a lack of resources and skills as barriers to providing CVD preventative care post-HDP. The survey with women after HDP revealed that women with a history of HDP are more likely to be assessed for blood pressure than lifestyle CVD risk factors, and that the women's barriers to obtaining care included difficulty obtaining an appointment and time required for attending appointments. Strategies to improve CVD preventative care were consistent between surveys, where 70% of GPs and 59% of women chose 'increasing women's awareness of increased CVD risk' and 67% of GPs and 55% of women chose 'improving communication between hospitals and primary care' as their preferred strategies. While the findings suggest that women with a history of HDP are receiving advice consistent with guidelines for traditional CVD risk markers, such as blood pressure, they are less likely to receive CVD preventative care for lifestyle or female-specific CVD risk factors.

Clinical efficacy of low-dose aspirin combined with calcium in preventing preeclampsia: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of low-dose aspirin combined with calcium supplements for the prevention of preeclampsia. METHODS: China National Knowledge Infrastructure, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library databases were searched from inception until December 2022. Randomized controlled trials investigating the preventive use of aspirin in combination with calcium supplementation for preeclampsia in high-risk pregnant women were included. The quality of the literature was evaluated, and a meta-analysis was conducted using RevMan 5.3 software to analyze the clinical efficacy of low-dose aspirin combined with calcium supplementation in preventing preeclampsia. RESULTS: Seven randomized controlled trials were included in this meta-analysis, and compared with the control group, the experimental group had lower incidence rates of preeclampsia with gestational hypertension (odds ratios [OR]: 0.17, 95% confidence interval [CI]: 0.11-0.28), preeclampsia (OR: 0.20, 95% CI: 0.10-0.37), gestational hypertension (OR: 0.15, 95% CI: 0.07-0.31), preterm birth (OR: 0.26, 95% CI: 0.16-0.44), postpartum hemorrhage (OR: 0.15, 95% CI: 0.08-0.27), and fetal growth restriction (OR: 0.16, 95% CI: 0.08-0.33). CONCLUSION: Compared with aspirin alone, low-dose aspirin combined with calcium supplementation was more effective in preventing preeclampsia, reduced the risk of preterm birth and postpartum hemorrhage, and promoted fetal growth. This intervention has clinical value and should be considered for high-risk pregnant women.

Lifestyle interventions to prevent adverse pregnancy outcomes in women at high risk for gestational diabetes mellitus: a randomized controlled trial.

Objective: To examine the effects of lifestyle interventions, including dietary guidance, health education and weight management, on pregnancy outcomes in women at high risk of gestational diabetes mellitus (GDM). Methods: Our study included 251 women at high risk of GDM and 128 randomized to lifestyle interventions (dietary guidance, health education, and weight management); One hundred and twenty-three people were randomly assigned to a control group (regular pregnancy check-ups). Counts between groups were compared using either chi-square test or Fisher's exact test. Results: Compared with the control group, the risk of GDM was reduced by 46.9% (16.4% vs 30.9%, P = 0.007) and the risk of pregnancy induced hypertension (PIH) was reduced by 74.2% (2.3% vs 8.9%, P = 0.034) in the intervention group. There were no significant differences in macrosomia, cesarean section, or preterm birth (P >0.05). Conclusion: The lifestyle intervention in this study helped pregnant women to better understand knowledge related to pregnancy, reduce stress and anxiety, and increase intake of adequate prenatal nutrition. This intervention prevented metabolic abnormalities that may occur due to inadequate nutrient intake during pregnancy. In addition, it helped women to control weight gain, maintain appropriate weight gain during pregnancy, and reduce the risk of excessive or insufficient weight gain, ultimately lowering the incidence of GDM and PIH. This highlights the importance of early screening and intervention for high-risk pregnant women. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2300073766.

Aspirin delays the onset of hypertensive disorders of pregnancy among nulliparous pregnant women: A secondary analysis of the ASPIRIN trial.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. DESIGN: Non-prespecified secondary analysis of a randomised masked trial of LDA. SETTING: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population-based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites-Belagavi and Nagpur) and Guatemala. POPULATION: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low-middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. METHODS: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). MAIN OUTCOME MEASURES: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. RESULTS: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02-1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17-0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49-0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94-1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67-0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64-1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33-0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). CONCLUSIONS: In this secondary analysis of a study of low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP.

Hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are one of the most commonly occurring complications of pregnancy and include chronic hypertension, gestational hypertension, and pre-eclampsia. New developments in early pregnancy screening to identify women at high risk for pre-eclampsia combined with targeted aspirin prophylaxis could greatly reduce the number of affected pregnancies. Furthermore, recent advances in the diagnosis of pre-eclampsia, such as placental growth factor based testing, have been shown to improve the identification of those pregnancies at highest risk of severe complications. Evidence from trials has refined the target blood pressure and timing of delivery to manage chronic hypertension and pre-eclampsia with non-severe features, respectively. Importantly, a wealth of epidemiological data now links HDP to future cardiovascular disease and diabetes decades after an affected pregnancy. This review discusses the current guidelines and research data on the prevention, diagnosis, management, and postnatal follow-up of HDP. It also discusses the gap in knowledge regarding the long term risks for cardiovascular disease following HDP and illustrates the importance of improving adherence to postnatal guidelines to monitor hypertension and the need for more research focused on primary prevention of future cardiovascular disease in women identified as being at high risk because of HDP.

Prevention and Screening for Cardiometabolic Disease Following Hypertensive Disorders in Pregnancy in Low-Resource Settings: A Systematic Review and Delphi Study.

Hypertensive disorders in pregnancy (HDP) and cardiometabolic and kidney diseases are rising in low- and middle-income countries (LMICs). While HDP are risk factors for cardiometabolic and kidney diseases, cost-effective, scalable strategies for screening and prevention in women with a history of HDP are lacking. Existing guidelines and recommendations require adaptation to LMIC settings. This article aims to generate consensus-based recommendations for the prevention and screening of cardiometabolic and kidney diseases tailored for implementation in LMICs. We conducted a systematic review of guidelines and recommendations for prevention and screening strategies for cardiometabolic and chronic kidney diseases following HDP. We searched PubMed/Medline, Embase and Cochrane Library for relevant articles and guidelines published from 2010 to 2021 from both high-income countries (HICs) and LMICs. No other filters were applied. References of included articles were also assessed for eligibility. Findings were synthesized narratively. The summary of guiding recommendations was subjected to two rounds of Delphi consensus surveys with experts experienced in LMIC settings. Fifty-four articles and 9 guidelines were identified, of which 25 were included. Thirty-five clinical recommendations were synthesized from these and classified into six domains: identification of women with HDP (4 recommendations), timing of first counseling and provision of health education (2 recommendations), structure and care setting (12 recommendations), information and communication needs (5 recommendations), cardiometabolic biomarkers (8 recommendations) and biomarkers thresholds (4 recommendations). The Delphi panel reached consensus on 33 final recommendations. These recommendations for health workers in LMICs provide practical and scalable approaches for effective screening and prevention of cardiometabolic disease following HDP. Monitoring and evaluation of implementation of these recommendations provide opportunities for reducing the escalating burden of noncommunicable diseases in LMICs.

Effectiveness of extended postpartum inpatient monitoring for hypertensive disorders of pregnancy to reduce the risk of readmission for preeclampsia with severe features.

BACKGROUND: Preeclampsia is an obstetrical disorder, which complicates 3% to 6% of pregnancies and contributes to 21.6% of readmissions in the postpartum period. The optimal strategy for inpatient monitoring of blood pressures to minimize readmissions for postpartum patients with hypertensive disorders is not known. We hypothesized that extended monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after the last blood pressure that was ≥150/100 mm Hg would result in decreased readmission rates for preeclampsia with severe features compared with those who were not observed by these blood pressure goals. OBJECTIVE: This study aimed to evaluate whether extended inpatient monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after their last blood pressure that was ≥150/100 mm Hg would improve readmission rates for preeclampsia with severe features within 6 weeks of delivery. STUDY DESIGN: This was a retrospective cohort study in patients with a singleton pregnancy and a diagnosis of a hypertensive disorder of pregnancy at their delivery admission or at any point during pregnancy who delivered 1 year before and 1 year after the implementation of extended inpatient monitoring of postpartum hypertension. The primary outcome was readmission for preeclampsia with severe features within 6 weeks of delivery. The secondary outcomes were length of stay during first admission, number of readmissions for any indication, intensive care unit admission, postpartum day at readmission, median systolic blood pressure in the 24-hour period before discharge, median diastolic blood pressure in the 24-hour period before discharge, intravenous antihypertensive medication required during first admission, and intravenous antihypertensive medication required during second admission. Univariable analysis was performed for the association between baseline maternal characteristics and the primary outcome. Multivariable analysis was performed, adjusting for baseline maternal characteristic differences between exposure groups. RESULTS: A total of 567 patients met the inclusion criteria of which 248 patients delivered before and 319 delivered after the implementation of extended monitoring. For baseline characteristics, the extended monitoring group had a significantly higher proportion of patients who were non-Hispanic Black and Hispanic, more diagnoses of hypertensive disorders and/or diabetes mellitus at the time of admission for delivery, a difference in the distribution of hypertensive diagnoses at the time of discharge from the first admission, and fewer discharged patients from their first admission on labetalol than the preintervention group. In a univariable analysis of the primary outcome, there was a significantly increased risk of readmission for preeclampsia with severe features in the extended monitoring group (62.5% vs 96.2% of total readmissions; P=.004). In multivariable analysis, patients in the extended monitoring group were more likely to be readmitted for preeclampsia with severe features than patients in the preintervention group (adjusted odds ratio, 3.45; 95% confidence interval, 1.03-11.5; P=.044). CONCLUSION: Extended monitoring with a strict blood pressure goal of <150/<100 mm Hg did not decrease readmissions for preeclampsia with severe features in patients with a previous diagnosis of a hypertensive disorder of pregnancy.

Effectiveness of a structured exercise intervention in gestational weight gain in pregnant women with overweight and obesity: A systematic review with meta-analysis.

OBJECTIVES: To assess the effectiveness of exercise interventions during pregnancy in managing gestational weight gain (GWG), excessive GWG, gestational diabetes (GD), hypertensive disorders, 2-h post-oral glucose tolerance test (OGTT), and birth weight in pregnant women with overweight/obesity (OW/OB). METHODS: The search strategy was conducted in five electronic databases, restricting to articles published within the past 10 years. Randomized controlled trials comparing exercise intervention with usual prenatal care in pregnant women with OW/OB were considered. Two reviewers extracted data and assessed the risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials and the quality of studies using Grading of Recommendations Assessment, Development and Evaluation classification. Continuous data were calculated as mean differences (MDs) and dichotomous data as risk ratios (RRs). RESULTS: Seven trials comprising 1648 pregnant women were included. Exercise interventions were associated with lower GWG (MD, -1.19 kg [95% confidence interval, CI, -1.79 to -0.60]) and lower incidence of GD (RR, 0.56 [95% CI, 0.40-0.78]). When analyzing excessive GWG, 2-h post-OGTT, birth weight, and hypertensive disorders, there was no statistically significant difference between the exercise and usual care groups. The strength of evidence was considered moderate. CONCLUSION: Exercise interventions during pregnancy in women with OW/OB were shown to influence GWG and the incidence of GD.

Hypertensive disorders of pregnancy pre- and postaspirin guideline publication in individuals with pregestational diabetes mellitus.

BACKGROUND: The US Preventive Services Taskforce published guidelines in 2014 recommending that low-dose aspirin be initiated between 12 and 28 weeks of gestation among high-risk patients for preeclampsia prophylaxis. Moreover, low-dose aspirin is recommended by some clinicians for the prevention of preterm birth. OBJECTIVE: This study aimed to evaluate whether there is an association between the US Preventive Services Taskforce aspirin guideline hypertensive disorders of pregnancy and the rates of hypertensive disorders of pregnancy and preterm birth in individuals with pregestational diabetes mellitus. STUDY DESIGN: This was a repeated cross-sectional analysis of individuals with pregestational diabetes mellitus and at least 1 singleton delivery at >20 weeks of gestation with records available in the National Vital Statistics System between 2010 and 2018. The primary outcome was hypertensive disorders of pregnancy, and the secondary outcome was preterm birth. Demographics and clinical characteristics among individuals in the pre-US Preventive Services Taskforce guideline cohort (2010-2013) were compared with that of individuals in the post-US Preventive Services Taskforce guideline cohort (2015-2018). Multivariable regression estimated the odds ratios and 95% confidence intervals for the association between guideline publication and the selected endpoints. Effect modification was assessed for access to prenatal care using the Kotelchuck Index (<80% vs ≥80%). Furthermore, a sensitivity analysis limited to nulliparas was performed. RESULTS: Overall, 224,065 individuals were included. Individuals in the post-US Preventive Services Taskforce guideline cohort were more likely to be older, be obese, and have a history of preterm birth. In unadjusted and adjusted modeling, delivery in the post-US Preventive Services Taskforce guideline cohort was associated with hypertensive disorders of pregnancy (adjusted odds ratio, 1.25; 95% confidence interval, 1.22-1.28) and preterm birth (adjusted odds ratio, 1.10; 95% confidence interval, 1.08-1.12). The adjusted odds ratios for hypertensive disorders of pregnancy and preterm birth were more pronounced among those with less than adequate access to care. The findings were similar in the sensitivity analysis of only nulliparas. CONCLUSION: Delivery after US Preventive Services Taskforce aspirin guideline publication was associated with higher rates of hypertensive disorders of pregnancy and preterm birth in a population of individuals with diabetes mellitus. It is unknown whether patient or practitioner factors, or other changes in obstetrical care, contributed to these findings.

Exercise during pregnancy for preventing gestational diabetes mellitus and hypertensive disorders: An umbrella review of randomised controlled trials and an updated meta-analysis.

OBJECTIVE: This study aimed to provide, through an umbrella review, an overview of the effect of single exercise interventions during pregnancy on gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Also, to update the current evidence through an updated meta-analysis. DESIGN: Umbrella review. SETTING: PubMed, EMBASE, Web of Science, Cochrane database of systematic reviews, Epistemonikos, SPORTDiscus, Clinicaltrials.gov, and PROSPERO register were searched from the database inception until August 2021. POPULATION: Peer-reviewed systematic reviews and meta-analyses of randomised controlled trials (RCTs) and RCTs samples. METHODS: Random-effects model was used to calculate relative risk with 95% confidence interval in the updated meta-analysis. The reference category was the groups that received usual prenatal care. AMSTAR 2 and the Cochrane Collaboration tool were used to assess the quality and GRADE approach was used to assess the overall certainly of evidence. MAIN OUTCOME MEASURES: GDM and HDP relative risk. RESULTS: Twenty-three systematic reviews and meta-analyses; and 63 RCTs were included. Single exercise interventions reduced the incidence of GDM and HDP in most systematic reviews and meta-analyses. Moreover, exercise interventions during pregnancy decrease the incidence of developing GDM and GH, particularly when they are supervised, have a low to moderate intensity level, and are initiated during the first trimester of pregnancy. CONCLUSION: Based on the findings, obstetric and physical exercise professionals could recommend exercise interventions during pregnancy as an effective strategy to improve maternal outcomes.

Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review.

PURPOSE: Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy. METHODS: A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta. RESULTS: A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied. CONCLUSION: We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.

Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets.

BACKGROUND: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. METHODS: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. RESULTS: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. CONCLUSIONS: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.