Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Ambient air pollution and hypertensive disorders of pregnancy in Rome.

BACKGROUND: Ambient air pollution has been associated with hypertensive disorders of pregnancy (HDP), but few studies rely on assessment of fine-scale variation in air quality, specific subtypes and multi-pollutant exposures. AIM: To study the impact of long-term exposure to individual and mixture of air pollutants on all and specific subtypes of HDP. METHODS: We obtained data from 130,470 liveborn singleton pregnacies in Rome during 2014-2019. Spatiotemporal land-use random-forest models at 1 km spatial resolution assigned to the maternal residential addresses were used to estimate the exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3). RESULTS: For PM2.5, PM10 and NO2, there was suggestive evidence of increased risk of preeclampsia (PE, n = 442), but no evidence of increased risk for all subtypes of HDP (n = 2297) and gestational hypertension (GH, n = 1901). For instance, an interquartile range of 7.0 µg/m3 increase in PM2.5 exposure during the first trimester of pregnancy was associated with an odds ratio (OR) of 1.06 (95% confidence interval: 0.81, 1.39) and 1.04 (0.92, 1.17) after adjustment for NO2 and the corresponding results for a 15.7 µg/m3 increase in NO2 after adjustment for PM2.5 were 1.11 (0.92, 1.34) for PE and 0.83 (0.76, 0.90) for HDP. Increased risks for HDP and GH were suggested for O3 in single-pollutant models and for PM after adjustment for NO2, but all other associations were stable or attenuated in two-pollutant models. CONCLUSIONS: The results of our study suggest that PM2.5, PM10 and NO2 increases the risk of PE and that these effects are robust to adjustment for O3 while the increased risks for GH and HDP suggested for O3 attenuated after adjustment for PM or NO2. Additional studies are needed to evaluate the effects of source-specific component of PM on subtypes as well as all types of HDP which would help to target preventive actions.

Gestational hypertension, preeclampsia, and gestational diabetes mellitus after high exposure to perfluoroalkyl substances from drinking water in Ronneby, Sweden.

BACKGROUND: Leakage of fire-fighting foam from an airfield caused contamination of the drinking water supplied to a third of the population in Ronneby, resulting in very high serum levels of predominantly perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS). The results of studies investigating the association between exposure to perfluorinated alkyl substances (PFAS) and pregnancy complications are inconsistent, and studies at high exposures of PFOS and PFHxS are lacking. OBJECTIVES: To investigate the association between exposure to high levels of PFAS and gestational hypertension and preeclampsia, and gestational diabetes mellitus. METHODS: We retrieved data on 27 292 childbirths between 1995 and 2013 from the National Medical Birth Register for women that had a residential address in Blekinge county for at least one year before delivery. Residential history was used as a proxy for exposure by categorizing women into high-, intermediate-, or background exposed based on their residential address during the five-year period before childbirth. Data on confounders were retrieved from administrative registers. The outcomes were defined based on International Classification of Diseases codes. We used logistic regression to estimate odds ratios (OR) for gestational hypertension and preeclampsia, and gestational diabetes mellitus. We also investigated effect modification by fetal sex. RESULTS: We found no evidence of increased risk of gestational hypertension and preeclampsia (OR 0.80; CI 0.63-1.03), nor gestational diabetes (OR 1.03; CI 0.67-1.58) after high PFAS exposure. There was no effect modification by fetal sex. DISCUSSION: This was the first study to investigate the association between high exposure to PFOS and PFHxS and pregnancy complications. The results from this study add important knowledge to public health management as new hotspots with high levels of PFAS are continuously discovered.

Restoring Angiotensin Type 2 Receptor Function Reverses PFOS-Induced Vascular Hyper-Reactivity and Hypertension in Pregnancy.

Perfluorooctane sulfonic acid (PFOS) exposure during pregnancy induces hypertension with decreased vasodilatory angiotensin type-2 receptor (AT2R) expression and impaired vascular reactivity and fetal weights. We hypothesized that AT2R activation restores the AT1R/AT2R balance and reverses gestational hypertension by improving vascular mechanisms. Pregnant Sprague-Dawley rats were exposed to PFOS through drinking water (50 µg/mL) from gestation day (GD) 4-20. Controls received drinking water with no detectable PFOS. Control and PFOS-exposed rats were treated with AT2R agonist Compound 21 (C21; 0.3 mg/kg/day, SC) from GD 15-20. In PFOS dams, blood pressure was higher, blood flow in the uterine artery was reduced, and C21 reversed these to control levels. C21 mitigated the heightened contraction response to Ang II and enhanced endothelium-dependent vasorelaxation in uterine arteries of PFOS dams. The observed vascular effects of C21 were correlated with reduced AT1R levels and increased AT2R and eNOS protein levels. C21 also increased plasma bradykinin production in PFOS dams and attenuated the fetoplacental growth restriction. These data suggest that C21 improves the PFOS-induced maternal vascular dysfunction and blood flow to the fetoplacental unit, providing preclinical evidence to support that AT2R activation may be an important target for preventing or treating PFOS-induced adverse maternal and fetal outcomes.

Risk of Hypertensive Disorders of Pregnancy in Women Treated With Serotonin-Norepinephrine Reuptake Inhibitors: A Comparative Study Using the EFEMERIS Database.

Background: Among antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) are particularly expected to increase the risk of hypertensive disorders of pregnancy (HDP) with regard to their biological mechanism. We aimed to evaluate the association between prenatal exposure to SNRI and HDP.Methods: In EFEMERIS, a French database including pregnant women covered by the French Health Insurance System of Haute-Garonne (2004-2019), we compared the incidence of HDP among women exposed to SNRI monotherapy during the first trimester of pregnancy to the incidence among 2 control groups: (1) women exposed to selective serotonin reuptake inhibitor (SSRI) monotherapy during the first trimester and (2) women not exposed to antidepressants during pregnancy. We conducted crude and also multivariate logistic regressions.Results: Of the 156,133 pregnancies, 143,391 were included in the study population, including 210 (0.1%) in the SNRI group, 1,316 (0.9%) in the SSRI group, and 141,865 (98.9%) in the unexposed group. After adjustment for depression severity and other mental conditions, the risk of HDP was significantly higher among women exposed to SNRIs (n = 20; 9.5%) compared to women exposed to SSRIs (n = 72; 5.5%; adjusted odds ratio [aOR] [95% CI] = 2.32 [1.28-4.20]) and to unexposed women (n = 6,224; 4.4%; aOR [95% CI] = 1.89 [1.13-3.18]).Conclusion: This study indicated an increased risk of HDP in women treated with SNRIs versus women treated with SSRIs.

Perfluoroalkyl and polyfluoroalkyl substances and hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and preeclampsia (PE), cause significant morbidity and mortality among pregnant women. Several environmental toxins, particularly those that affect the normal function of the placenta and the endothelium, are emerging as potential risk factors for HDP. Among them, per- and polyfluoroalkyl substances (PFAS), widely used in a variety of commercial products, have been related to a variety of adverse health effects including HDP. This study was conducted by searching three databases for observational studies reporting associations between PFAS and HDP, all of which were published before December 2022. We used random-effects meta-analysis to calculate pooled risk estimates, and assessing each combination of exposure and outcome for quality and level of evidence. In total, 15 studies were included in the systematic review and meta-analysis. The results from meta-analyses showed that risk of PE was increased with exposure to PFOA (perfluorooctanoic acid) (RR = 1.39, 95% CI = 1.05, 1.85; N = 6 studies; exposure = 1 ln-unit increment; low certainty), PFOS (perfluorooctane sulfonate) (RR = 1.51, 95% CI = 1.23, 1.86; N = 6 studies; exposure = 1 ln-unit increment; moderate certainty), and PFHxS (perfluorohexane sulfonate) (RR = 1.39, 95% CI = 1.10, 1.76; N = 6 studies; exposure = 1 ln-unit increment; low certainty). PFOS was also associated with an increased risk of HDP (RR = 1.39, 95% CI = 1.10, 1.76; exposure = 1 ln-unit increment; low certainty). Exposure to legacy PFAS (PFOA, PFOS, PFHxS) is associated with an increased risk of PE, and PFOS is further associated with HDP. In view of the limitations of meta-analysis and quality of evidence, these findings should be interpreted with caution. Further research is required that assesses exposure to multiple PFAS in diverse and well-powered cohorts.

Associations of periconceptional oral contraceptive use with pregnancy complications and adverse birth outcomes.

BACKGROUND: Periconceptional use of oral contraceptives (OCs) has been reported to increase risks of pregnancy complications and adverse birth outcomes, but risks are suggested to differ depending on the timing of discontinuation, amount of oestrogen and progestin content. METHODS: Prospective cohort study among 6470 pregnancies included in the PRegnancy and Infant DEvelopment (PRIDE) Study in 2012-19. Exposure was defined as any reported use of OCs within 12 months pre-pregnancy or after conception. Outcomes of interest were gestational diabetes, gestational hypertension, pre-eclampsia, pre-term birth, low birthweight and small for gestational age (SGA). Multivariable Poisson regression using stabilized inverse probability weighting estimated relative risks (RRs) with 95% CIs. RESULTS: Any periconceptional OC use was associated with increased risks of pre-eclampsia (RR 1.38, 95% CI 0.99-1.93), pre-term birth (RR 1.38, 95% CI 1.09-1.75) and low birthweight (RR 1.45, 95% CI 1.10-1.92), but not with gestational hypertension (RR 1.09, 95% CI 0.91-1.31), gestational diabetes (RR 1.02, 95% CI 0.77-1.36) and SGA (RR 0.96, 95% CI 0.75-1.21). Associations with pre-eclampsia were strongest for discontinuation 0-3 months pre-pregnancy, for OCs containing ≥30 µg oestrogen and for first- or second-generation OCs. Pre-term birth and low birthweight were more likely to occur when OCs were discontinued 0-3 months pre-pregnancy, when using OCs containing <30 µg oestrogen and when using third-generation OCs. Associations with SGA were observed for OCs containing <30 µg oestrogen and for third- or fourth-generation OCs. CONCLUSIONS: Periconceptional OC use, particularly those containing oestrogen, was associated with increased risks of pre-eclampsia, pre-term birth, low birthweight and SGA.

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

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

Labetalol, Low-dose Aspirin, and Vitamin E and Calcium for Gestational Hypertension and Influence on MicroRNA-126 and PLGF Levels.

Context: Hypertensive disorders in pregnancy (HDP) are common complications of pregnancy and the main cause of perinatal adverse outcomes. Clinicians mostly adopt comprehensive treatment strategies, including anticoagulants and micronutrients. At present, the clinical effects of a strategy combining labetalol + low-dose aspirin + vitamin E and calcium aren't completely clear. Objective: The study intended to investigate the efficacy of a combined therapy of labetalol + low-dose aspirin + vitamin E and calcium for the treatment of HDP and the relationship of the levels of expression of microRNA-126 and placenta growth factor (PLGF) to outcomes, to provide better treatment strategies for patients. Design: The research team performed a randomized controlled trial. Setting: The study took place in the Department of Obstetrics and Gynecology at Jinan Maternity and Child Care Hospital in Jinan, China. Participants: Participants were 130 HDP patients at the hospital between July 2020 and September 2022. Intervention: The research team divided participants into two groups, with 65 participants each, using the random number table method: (1) a control group that received a combined therapy of labetalol + vitamin E and calcium and (2) an intervention group that received a combined therapy of labetalol + low-dose aspirin + vitamin E and calcium. Outcome Measures: The research team measured clinical efficacy, blood pressure parameters, 24 h urinary protein, microRNA-126, PLGF, and drug-related adverse reactions. Results: The intervention group's efficacy rate was 96.92%, which was significantly higher than that of the control group at 83.08% (P = .009). Postintervention, the intervention group's systolic blood pressure, diastolic blood pressure, and 24 h urinary protein levels were significantly lower than those of the control group (all P < .05), while the microRNA-126 and PLGF levels were significantly higher (both P < .05). No significant differences existed in the rate of drug-related adverse reactions between the groups, at 4.62% and 6.15%, respectively (P > 0.05). Conclusions: The combined therapy of labetalol + low-dose aspirin + vitamin E and calcium had a high efficacy rate and could significantly reduce blood pressure and 24h urine protein and significantly increase microRNA-126 and PLGF levels, with a high safety profile.

Maternal exposure to ozone and risk of gestational hypertension and eclampsia in the United States.

BACKGROUND: Exposure to ambient ozone during pregnancy may be linked with hypertensive disorders in pregnancy, but evidence is largely unknown. We aimed to estimate the association between maternal exposure to ozone and risk of gestational hypertension and eclampsia in the contiguous United States (US). METHODS: We included 2,393,346 normotensive mothers aged from 18 to 50 years old who had a live singleton birth documented in the National Vital Statistics system in the US in 2002. We obtained information on gestational hypertension and eclampsia from birth certificates. We estimated daily ozone concentrations from a spatiotemporal ensemble model. We used distributed lag model and logistic regression to estimate the association between monthly ozone exposure and risk of gestational hypertension or eclampsia after adjusting for individual-level covariates and county poverty rate. RESULTS: Of the 2,393,346 pregnant women, there were 79,174 women with gestational hypertension and 6034 with eclampsia. A 10 parts per billion (ppb) increase in ozone was associated with an increased risk of gestational hypertension over 1-3 months before conception (OR = 1.042, 95 % CI: 1.029, 1.056), 2-3 months after conception (OR = 1.058, 95 % CI: 1.040, 1.077), and 3-5 months after conception (OR = 1.031, 95 % CI: 1.018, 1.044). The corresponding OR for eclampsia was 1.115 (95 % CI: 1.074, 1.158), 1.048 (95 % CI: 1.020, 1.077), and 1.070 (95 % CI: 1.032, 1.110), respectively. CONCLUSIONS: Exposure to ozone was associated with an increased risk of gestational hypertension or eclampsia, especially during 2 to 4 months after conception.

Exposure to endocrine-disrupting chemicals and risk of gestational hypertension and preeclampsia: A systematic review and meta-analysis.

Prenatal exposure to endocrine-disrupting chemicals has been linked to gestational hypertension (GH) and preeclampsia (PE). However, the results were conflicting and inconclusive. We conducted a systematic review and meta-analysis for an overview of these relationships. We searched PubMed, and Google Scholar for studies investigating bisphenol A, phthalates, and per or poly-fluoroalkyl substances and GH or PE. Pooled odds ratio (OR) with a 95% confidence interval (CI) were calculated for risk estimate using the generic inverse variance method. A total of 14 studies were included in the present analysis. The pooled results demonstrated that perfluorooctanoic acid (PFOA, OR:1.20, 95% CI: 1.04, 1.39), perfluoro octane sulfonic acid (PFOS, (OR:1.23, 95% CI: 1.10, 1.38), and perfluononanoic acid (PFNA, OR:1.20, 95% CI: 1.03, 1.40) were significantly associated with an increased risk of PE. There was no significant association observed with perfluoro hexane sulfonic acid (PFHxS), perfluoro decanoic acid (PFDA), perfluoro heptanoic acid (PFHpA), and perfluoro undecanoic acid (PFUnDA) and PE. For GH, a statistically significant positive association was found with PFOA (OR:1.18, 95% CI: 1.01, 1.39) and PFHxS (OR:1.15, 95% CI: 1.02, 1.29). Among various phthalates analysed only mono-ethyl phthalate (MEP, OR:1.37, 95% CI: 1.11, 1.70) showed an association with GH. From our analysis, bisphenol A exposure during pregnancy did not show a significant association with the risk of PE. Our findings indicated that exposure to PFASs such as PFOA, PFOS, and PFNA during pregnancy is associated with an increased risk of PE and PFOA and PFHxS with GH. We also found that MEP was associated with GH. Most of the results were unstable in sensitivity analysis. Since most of these associations have limited evidence, more research is needed to confirm these findings.

Effects of fine ambient particulate matters on de novo hypertensive disorders of pregnancy and blood pressure before 20 weeks.

The effects of fine particulate matter (PM) on de novo hypertensive disorders of pregnancy (HDP) were inconsistent during the first and second trimesters. This study aimed to assess the trimester-specific effects of PM2.5 and PM1 prior to diagnosis of de novo HDP. The exposure of fine PM was predicted by satellite remote sensing data according to maternal residential addresses. De novo HDP was defined as gestational hypertension and preeclampsia during the current pregnancy. A logistic regression model was performed to assess the association of PM2.5 and PM1 with HDP during the first and early second trimesters (0-13 weeks and 14-20 weeks). The generalized estimating equation model was conducted to assess the effect of PM2.5 and PM1 on blood pressure. The present study included 22,821 pregnant women (mean age, 29.1 years) from 2013 to 2017. PM2.5 and PM1 were significantly associated with an increased risk of de novo HDP during the first trimester (OR = 1.070, 95% CI: 1.013-1.130; OR = 1.264, 95% CI: 1.058-1.511 for per 10 µg/m3) and early second trimester (OR = 1.045, 95% CI: 1.003-1.088; OR = 1.170, 95% CI: 1.002-1.366 for per 10 µg/m3). Significant trends of increased de novo HDP risk was also observed with the increment of PM (all P for trend <0.05). The stratified analyses demonstrated that the associations between exposure to fine PM and the risk of HDP were more pronounced among the pregnant women with maternal age above 35 and low maternal education level (all OR >1.047). Each 10 µg/m3 increase of PM1 and PM2.5 before diagnosis of de novo HDP elevated 0.204 (95% CI: 0.098-0.310) and 0.058 (95%CI: 0.033-0.083) mmHg of systolic blood pressure. Exposure to PM2.5 and PM1 during the first and early second trimester were positively associated with the risk of de novo HDP. The fine PM before diagnosis of de novo HDP elevated the systolic blood pressure.

Effects of Nifedipine and Labetalol Combined with Magnesium Sulfate on Blood Pressure Control, Blood Coagulation Function, and Maternal and Infant Outcome in Patients with Pregnancy-Induced Hypertension.

Objective: The purpose is to investigate the influence of nifedipine, labetalol, and magnesium sulfate on blood pressure control, blood coagulation, and maternal and infant outcome in those suffering from pregnancy-induced hypertension (PIH). Methods: From January 2019 to April 2021, 100 participants with PIH in our center were randomly assigned to a control group and a research group. As a control, nifedipine combined with magnesium sulfate was administered. Nifedipine, labetalol, and magnesium sulfate were administered to the research group. The curative effect, blood pressure level, blood coagulation function, vascular endothelial function, and pregnancy comparisons were made between the two groups. Results: Based on the results of the study, the effective rate totaled 92.00%, while as for the control group, it was 80.0%, which indicates that there was a statistically significant difference between the effective rates of the research group and that of the control group, and the difference was statistically significant (P < 0.05). Blood pressure and blood coagulation function did not differ significantly between the two groups before treatment, and the difference was not statistically significant (P > 0.05). After treatment, both groups experienced a significant drop in systolic and diastolic blood pressure. After treatment, a higher PT index was found in the research group than in the control group. Likewise, the Fbg, D-D, and PLT were lower compared to those in the control group, and the difference was statistically significant (P < 0.05). Neither group had significantly different vascular endothelial function before treatment, and the difference was not statistically significant (P > 0.05). After treatment, the ET-1 of the two groups decreased, and the level of NO increased. There was a lower ET-1 in the research group than in the control group as well as a higher NO level in the research group than in the control group, and the difference was statistically significant (P < 0.05). Compared with the pregnancy outcome, in comparison to the controls, the research group had a higher vaginal delivery rate. Significantly, fewer cases of fetal distress, intrauterine asphyxia, and placental abruption were reported in the research group than in the control group, and the difference was statistically significant (P < 0.05). Conclusion: Nifedipine, in combination with magnesium sulfate and labetalol, is effective at treating PIH, reducing blood pressure, improving blood coagulation, preventing cardiovascular events and vascular endothelial function, and further improve the pregnancy outcome.

The association between caffeine exposure during pregnancy and risk of gestational hypertension/preeclampsia: A meta-analysis and systematical review.

BACKGROUND: The potential effect of caffeine exposure during pregnancy on gestational hypertension (GH)/preeclampsia has attracted attention but remains unclear. METHODS: A systematic literature search of PubMed, Embase, and Cochrane Library databases was performed until March 2022. Observational studies assessing the association between caffeine exposure during pregnancy and the risk of GH/preeclampsia were included. The study protocol was registered in PROSPERO: CRD42022322387. RESULTS: Ten studies involving 114 984 pregnant women (2548 diagnosed with GH and 2473 diagnosed with preeclampsia) were included. Comparing caffeine exposure with noncaffeine exposure, no significant association was found between caffeine exposure during pregnancy and the risk of GH (odds ratio [OR] = 0.99, 95% confidence interval [CI]: 0.90-1.08, p = 0.800) and preeclampsia (OR = 1.13, 95% CI: 0.97-1.31, p = 0.114). Subgroup analyses comparing low to moderate doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.00, p = 0.987) or preeclampsia (OR = 1.03, p = 0.648). Besides, subgroup analyses comparing high doses with no/lowest doses showed that caffeine exposure during pregnancy was not significant associated with GH (OR = 1.06, p = 0.623) or preeclampsia (OR = 1.18, p = 0.192). CONCLUSION: This study found that caffeine exposure during pregnancy was not significantly associated with the risk of GH/preeclampsia.

Associations of perfluoroalkyl and polyfluoroalkyl substances with gestational hypertension and blood pressure during pregnancy: A cohort study.

Previous studies have reported inconsistent associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and gestational hypertension (GH) and blood pressure (BP) during pregnancy. Herein, we aimed to evaluate individual and overall effects of PFAS on GH and longitudinal BP measures during pregnancy. We included 826 pregnant women from the Jiashan Birth Cohort established between 2016 and 2018. Concentrations of thirteen PFAS were quantified using plasma samples collected within 16 weeks of gestation. Longitudinal BP measures were obtained from medical records, and more than nine measurements were available for 85.60% of participants. GH was defined as new-onset hypertension occurring after 20 weeks of gestation. Logistic regression models were used to examine the effect of PFAS on GH, while generalized estimating equation models evaluated the average effect of PFAS on BP in each trimester. The potential effect modification by fetal sex was also examined. Bayesian kernel machine regression (BKMR) and quantile g-computation (QgC) were implemented to explore the overall effect of the PFAS mixture. PFOA, PFOS, and PFHxS presented the highest median concentrations of 11.99, 8.81 and 5.43 ng/mL, respectively. Overall, 5.57% of subjects developed GH. PFOS, PFDA, PFUdA, and PFDoA were significantly associated with lower GH odds, and odds ratios ranged between 0.62 and 0.68. We noted associations between PFAS and lower systolic BP and diastolic BP in the third trimester, with PFDA and PFUdA exhibiting the effect on systolic BP only in pregnant women carrying a female fetus. These associations were further confirmed by BKMR and QgC, showing an inverse overall effect of the PFAS mixture. Higher concentrations of PFAS during early pregnancy were associated with lower GH risk and longitudinal BP measures in the third trimester in a population with relatively high exposure levels. Fetal sex might modify the effects of PFDA and PFUdA on systolic BP in the third trimester.

Associations of pregnancy complications with ambient air pollution in China.

BACKGROUND: Gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are common pregnancy complications and can result in maternal and prenatal morbidity and mortality. Air pollution exposure could adversely impact pregnancy complications; however, evidence remains limited in China, where ambient air pollution is relatively severe. OBJECTIVE: This study aims to examine the associations of GH, PE, and GDM with exposure to six air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) during pregnancy. METHODS: Leveraging a multicenter birth cohort study among pregnant women in 24 hospitals from 15 provinces in China, we obtained data for maternal characteristics and pregnancy outcomes. We generated ambient concentrations of the six air pollutants using a combination of chemical transport model simulations with monitoring data. We used multivariable logistic regression models to estimate the effects on pregnancy complications from exposure to six air pollutants in each trimester and the entire pregnancy. RESULTS: Among the total 3754 pregnant women in this study, the prevalences of GH, GDM, and PE were 2.6 %, 11.2 %, and 0.7 %, respectively. GH risk increased 11.9 % (95 % CI, -8.5 %, 36.8 %) and 13.8 % (1.4 %, 27.8 %) per 10 µg/m3 increases in PM2.5 and PM10 in the entire pregnancy, respectively. PM2.5 and PM10 exposures in the first trimester were significantly associated with an increased risk of GDM. Exposure to O3, SO2, NO2, and CO in early pregnancy could be associated with GDM risk. Geographic region and season of conception may influence the associations of GH and PE with air pollution. CONCLUSIONS: Ambient particulate matter pollution adversely affects GH, GDM, and PE among Chinese pregnant women. Since most regions of China still suffer from hazardous levels of air pollution, our findings indicate importance of better protecting pregnant women from the risk of air pollution.

Effects of Misoprostol on Induction of Labour in Patients with Hypertensive Disorders of Pregnancy: A Meta-Analysis.

Objective: Hypertensive disorders of pregnancy (HDP) can cause serious prenatal and postnatal complications and is a threat to maternal and fetal health. To offer guidance for clinical decisions, we systematically reviewed the effects of misoprostol on induction of labour in HDP patients. Methods: PubMed, Web of Science, Embase, CNKI, and Wanfang databases were searched for relevant literature from 2010 to 2020. Subsequently, a meta-analysis was performed to compare the effective rate of induction of labour and reducing postpartum hemorrhage (PPH) between the intervention group (n = 544, misoprostol) and the control group (n = 543, oxytocin). Results: A total of 10 studies with 1087 patients were included. The 10 studies compared the effective rate of induction of labour between the two groups and confirmed that the effective rate in the intervention group was significantly higher than that in the control group (OR = 4.37; 95% CI: 2.73, 7.00). Seven studies compared PPH between the groups and showed that it was significantly reduced in the intervention group compared to the control group (SMD = -1.32; 95% CI: -2.05, -0.59; P < 0.0001). Conclusion: Misoprostol has a high effective rate of induction of labour in HDP patients and is an effective uterotonic agent in reducing PPH. This meta-analysis provides clinicians with meaningful information to help them make evidence-based decisions.

Paeoniflorin alleviates NG-nitro-L-arginine methyl ester (L-NAME)-induced gestational hypertension and upregulates silent information regulator 2 related enzyme 1 (SIRT1) to reduce H2O2-induced endothelial cell damage.

Pregnancy-induced hypertension (PIH) is a leading cause of maternal mortality. Paeoniflorin has been reported to alleviate hypertension, thus relieving the injury of target organ. This study aimed to investigate the role of paeoniflorin in PIH development by regulating SIRT1 in rats. The mean arterial pressure (MAP), urine protein and histopathological damage of placenta in gestational hypertension rats were, respectively, detected by noninvasive tail-artery pressure measuring instrument, BCA method and H&E staining. The viability of human umbilical vein endothelial cells (HUVECs) treated with paeoniflorin or/and H2O2 was observed by CCK-8 assay. SIRT1 protein expression in HUVECs treated with paeoniflorin or/and H2O2 was analyzed by Western blot. Tunel assay, wound healing assay and tube formation assay were used to detect the apoptosis, migration and tube formation of HUVECs administrated with paeoniflorin or/and H2O2 or/and EX527 (SIRT1 inhibitor). As a result, MAP, urine protein and histopathological damage of placenta were enhanced in PIH rats, which were then alleviated by paeoniflorin. Paeoniflorin decreased the levels of sFlt-1, PlGF and VEGF in serum and placental tissues of gestational hypertension rats as well as the inflammatory response and oxidative stress. In addition, paeoniflorin promoted the expressions of SIRT1 and NO/eNOS and inhibited the production of iNOS in gestational hypertension rats to improve vascular endothelial cell injury. However, SIRT1 inhibition could suppress the protective effects of paeoniflorin on endothelial dysfunction of H2O2-induced HUVECs. In conclusion, paeoniflorin could improve gestational hypertension development by upregulating SIRT1.

Combined Oral Contraceptive Pill-Induced Hypertension and Hypertensive Disorders of Pregnancy: Shared Mechanisms and Clinical Similarities.

PURPOSE OF REVIEW: Oral contraceptive pill-induced hypertension (OCPIH) and hypertensive disorders in pregnancy (HDP) share common risk factors and pathophysiological mechanisms, yet the bidirectional relationship between these two conditions is not well-established. We review and describe OCPIH and HDP to better understand how hormonal and metabolic imbalances affect hypertension. RECENT FINDINGS: Oral contraceptive pills continue to be a popular method of contraception, with an incidence of OCPIH ranging from 1-8.5% among OCP users. HDP have an incidence of 5-10% of all pregnancies in the USA and have been shown to be a powerful predictor of lifetime adverse cardiovascular outcomes, including future hypertension. OCPIH and HDP share common risk factors such as age, BMI, past personal and family history of hypertension, as well as pathogenic mechanisms, including alterations in hormonal metabolism and the renin angiotensin aldosterone system; imbalance of vasodilator-vasoconstrictor compounds; and changes in the cardiovascular system. Future research should address additional potential mechanisms that underlie hypertension in these two conditions where endocrine changes, either physiological (pregnancy) or iatrogenic (use of OCP), play a role. This may lead to novel, targeted treatment options to improve hypertension management and overall cardiovascular risk profile management in this subset of young female patients.

Considering environmental exposures to per- and polyfluoroalkyl substances (PFAS) as risk factors for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, lead to significant maternal morbidity and in some cases, maternal mortality. Environmental toxicants, especially those that disrupt normal placental and endothelial function, are emerging as potential risk factors for HDP. Per- and polyfluoroalkyl substances (PFAS) are a large group of ubiquitous chemicals found in consumer products, the environment, and increasingly in drinking water. PFAS have been associated with a multitude of adverse health effects, including dyslipidemia, hypertension, and more recently, HDP. In this review, we present epidemiological and mechanistic evidence for the link between PFAS and HDP and recommend next steps for research and prevention efforts. To date, epidemiological studies have assessed associations between only ten of the thousands of PFAS and HDP. Positive associations between six PFAS (PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFHxS, perfluorohexane sulfonic acid; PFHpA, perfluoroheptanoic acid; PFBS, perfluorobutanesulfonic acid; and PFNA, perfluoronanoic acid) and risk for HDP have been reported in some, but not all, studies. PFAS disrupt placental and immune function, cause oxidative stress, and disrupt lipid metabolism. These physiological disruptions may be mechanisms through which PFAS can lead to HDP. Overall, limited epidemiological evidence and plausible mechanisms support PFAS as risk factors for HDP. More research is needed in diverse, well-powered cohorts that assess exposures to as many PFAS as possible. Such research should consider not only individual PFAS but also the totality of exposures to PFAS and other environmental chemicals. Pregnant women may be a group that is vulnerable to PFAS exposure, and as such HDP risk should be considered by policymakers setting PFAS exposure limits. In the interim, medical and public health professionals in regions with PFAS contamination could provide short-term solutions in the form of patient-level prevention, increased monitoring, and early intervention for HDP.