RESUMO
BACKGROUND: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia. METHODS: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations. RESULTS: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it. CONCLUSIONS: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.
RESUMO
BACKGROUND: A parallel has been drawn between first-trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mm Hg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify the risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. OBJECTIVE: We evaluated the relationship between various blood pressure cutoffs at 11-13 weeks of gestation and the development of preeclampsia, overall and according to key maternal characteristics. STUDY DESIGN: This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals, 2006-2020. Blood pressure at 11-13 weeks of gestation was classified according to American College of Cardiology/American Heart Association categories (mm Hg) as (1) normal blood pressure (systolic <120 and diastolic <80), (2) elevated blood pressure (systolic ≥120 and diastolic <80), stage 1 hypertension (systolic ≥130 or diastolic 80-89), and stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen-positive rate, and positive and negative likelihood ratios, with 95% confidence intervals. A P value of <.05 was considered significant. RESULTS: There were 137,458 pregnancies screened at 11-13 weeks of gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with normal blood pressure, stage 2 hypertension was associated with both preterm preeclampsia (0.3% to 4.9%) and term preeclampsia (1.0% to 8.3%). A blood pressure threshold of 140/90 mm Hg was good at identifying women at increased risk of preeclampsia overall (positive likelihood ratio, 5.61 [95% confidence interval, 5.14-6.11]) and across maternal characteristics, compared with elevated blood pressure (positive likelihood ratio, 1.70 [95% confidence interval, 1.63-1.77]) and stage 1 hypertension (positive likelihood ratio, 2.68 [95% confidence interval, 2.58-2.77]). There were 2 exceptions: a blood pressure threshold of 130/80 mm Hg was better for the 2.1% of women with body mass index <18.5 kg/m2 (positive likelihood ratio, 5.13 [95% confidence interval, 3.22-8.16]), and a threshold of 135/85 mm Hg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio, 5.24, [95% confidence interval, 4.77-5.77]). There was no blood pressure threshold below which reassurance could be provided against the development of preeclampsia (all-negative likelihood ratios ≥0.20). CONCLUSION: The traditional blood pressure threshold of 140/90 mm Hg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however, a randomized trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold is reassured against the development of preeclampsia, regardless of maternal characteristics.
RESUMO
COVID-19 vaccination rates are lower in women of reproductive age (WRA), including pregnant/postpartum women, despite their poorer COVID-19-related outcomes. We evaluated the vaccination experiences of 3568 U.K. WRA, including 1983 women (55.6%) experiencing a pandemic pregnancy, recruited through the ZOE COVID Symptom Study app. Two staggered online questionnaires (Oct-Dec 2021: 3453 responders; Aug-Sept 2022: 2129 responders) assessed reproductive status, COVID-19 status, vaccination, and attitudes for/against vaccination. Descriptive analyses included vaccination type(s), timing relative to age-based eligibility and reproductive status, vaccination delay (first vaccination >28 days from eligibility), and rationale, with content analysis of free-text comments. Most responders (3392/3453, 98.2%) were vaccinated by Dec 2021, motivated by altruism, vaccination supportiveness in general, low risk, and COVID-19 concerns. Few declined vaccination (by Sept/2022: 20/2129, 1.0%), citing risks (pregnancy-specific and longer-term), pre-existing immunity, and personal/philosophical reasons. Few women delayed vaccination, although pregnant/postpartum women (vs. other WRA) received vaccination later (median 3 vs. 0 days after eligibility, p < 0.0001). Despite high uptake, concerns included adverse effects, misinformation (including from healthcare providers), ever-changing government advice, and complex decision making. In summary, most women in this large WRA cohort were promptly vaccinated, including pregnant/post-partum women. Altruism and community benefit superseded personal benefit as reasons for vaccination. Nevertheless, responders experienced angst and received vaccine-related misinformation and discouragement. These findings should inform vaccination strategies in WRA.
RESUMO
BACKGROUND: Maternity care services in the United Kingdom have undergone drastic changes due to pandemic-related restrictions. Prior research has shown maternity care during the pandemic was negatively experienced by women and led to poor physical and mental health outcomes in pregnancy. A synthesis is required of published research on women's experiences of maternity care during the latter half of the COVID-19 pandemic. AIM: To update a previous systematic review of maternity care experiences during the pandemic to June 2021, exploring experiences of maternity care specifically within the United Kingdom and how they may have changed, in order to inform future maternity services. METHODS: A systematic review of qualitative literature was conducted using comprehensive searches of five electronic databases and the Cochrane COVID Study Register, published between 1 June 2021 and 13 October 2022, and further updated to 30 September 2023. Thematic Synthesis was utilised for data synthesis. FINDINGS: Of 21,860 records identified, 27 studies were identified for inclusion. Findings included 14 descriptive themes across the five core concepts: (1)Care-seeking and experience; (2)Virtual care; (3)Self-monitoring; (4)COVID-19 vaccination; (5)Ethical future of maternity care. DISCUSSION: Our findings in the UK are consistent with those globally, and extend those of the previous systematic review, particularly about women's perceptions of the COVID-19 vaccine during pregnancy. CONCLUSION: Our findings suggest the following are important to women for future maternity care: personalisation and inclusiveness; clear and evidence-based communication to facilitate informed decision-making; and achieving balance between social commitments and time spent settling into motherhood.
Assuntos
COVID-19 , Serviços de Saúde Materna , Pesquisa Qualitativa , SARS-CoV-2 , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Reino Unido , Gravidez , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pandemias , Seguimentos , Satisfação do PacienteRESUMO
BACKGROUND: Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long-term (visit-to-visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long-term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes. METHODS AND RESULTS: Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short-term, not long-term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40-2.15], severe hypertension [1.40-2.20]), and fetal growth (small-for-gestational-age infants [1.12-1.32] or low birth weight [1.18-1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes. CONCLUSIONS: Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.
Assuntos
Hipertensão Induzida pela Gravidez , Hipertensão , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Pressão Sanguínea/fisiologia , Frequência Cardíaca , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Resultado da GravidezRESUMO
Preeclampsia (PE) poses a considerable risk to the long-term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions. Under hypoxia and H/R, intracellular total and non-esterified cholesterol levels were significantly increased. This coincided with an upregulation of HMG-CoA-reductase and HMG-CoA-synthase (key genes regulating cholesterol biosynthesis), and a decrease in acetyl-CoA-acetyltransferase-1 (ACAT1), which mediates cholesterol esterification. Hypoxia and H/R also increased the intracellular levels of reactive oxygen species and elevated the expression of hypoxia-inducible factor (HIF)-2α and sterol-regulatory-element-binding-protein (SREBP) transcription factors. Additionally, exposure of trophoblasts to hypoxia and H/R resulted in enhanced cholesterol efflux to maternal and fetal serum. This was accompanied by an increased expression of proteins involved in cholesterol transport such as the scavenger receptor class B type I (SR-BI) and the ATP-binding cassette transporter G1 (ABCG1). Despite these metabolic alterations, mitogen-activated-protein-kinase (MAPK) signaling, a key regulator of cholesterol homeostasis, was largely unaffected. Our findings indicate dysregulation of cholesterol homeostasis at multiple metabolic points in both the trophoblast hypoxia model and placentae from women with PE. The increased cholesterol efflux and intracellular accumulation of non-esterified cholesterol may have critical implications for both the mother and the fetus during pregnancy, potentially contributing to an elevated cardiovascular risk later in life.
Assuntos
Placenta , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Transporte Biológico , Hipóxia , HomeostaseRESUMO
OBJECTIVE: To compare pre-eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre-eclampsia prevention. DESIGN: Our search strategy provided hierarchical evidence of relationships between risk factors and pre-eclampsia using Medline (Ovid), searched from January 2010 to January 2021. SETTING: Published studies and CPGs. POPULATION: Pregnant women. METHODS: We evaluated the strength of association and quality of evidence (GRADE). CPGs (n = 15) were taken from a previous systematic review. MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Of 78 pre-eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually 'probable' (n = 40, 51.3%) and the quality of evidence was low (n = 35, 44.9%). The 'major' and 'moderate' risk factors proposed by 8/15 CPGs were not well aligned with the evidence; of the ten 'major' risk factors (alone warranting aspirin prophylaxis), associations with pre-eclampsia were definite (n = 4), probable (n = 5) or possible (n = 1), based on moderate (n = 4), low (n = 5) or very low (n = 1) quality evidence. Obesity ('moderate' risk factor) was definitely associated with pre-eclampsia (high-quality evidence). The other ten 'moderate' risk factors had probable (n = 8), possible (n = 1) or no (n = 1) association with pre-eclampsia, based on evidence of moderate (n = 1), low (n = 5) or very low (n = 4) quality. Three risk factors not identified by the CPGs had probable associations (high quality): being overweight; 'prehypertension' at booking; and blood pressure of 130-139/80-89 mmHg in early pregnancy. CONCLUSIONS: Pre-eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor of obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of the strategies advocated by CPGs is needed.
Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/prevenção & controle , Fatores de Risco , Pressão Sanguínea , ObesidadeRESUMO
OBJECTIVE: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level. DESIGN: An observational study. SETTING: Analysis of data from the population-based UK Southampton Women's Survey (SWS). POPULATION OR SAMPLE: 3003 SWS participants. METHODS: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. MAIN OUTCOME MEASURES: Gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission. RESULTS: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks' gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia and BP ≥140/90 mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule-in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05-1.39). CONCLUSIONS: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.
RESUMO
Following our first Special Issue, we are pleased to present this Special Issue in the International Journal of Molecular Sciences entitled 'Placental Related Disorders of Pregnancy 2 [...].
Assuntos
Placenta , Complicações na Gravidez , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Children from pregnancies affected by preeclampsia have an increased risk of cognitive and behavioral alterations via unknown pathophysiology. We tested the hypothesis that preeclampsia generated reduced brain cortex angiogenesis in the offspring. METHODS: The preeclampsia-like syndrome (PELS) mouse model was generated by administering the nitric oxide inhibitor NG-nitroarginine methyl ester hydrochloride. Confirmatory experiments were done using 2 additional PELS models. While in vitro analysis used mice and human brain endothelial cells exposed to serum of postnatal day 5 pups or umbilical plasma from preeclamptic pregnancies, respectively. RESULTS: We report significant reduction in the area occupied by blood vessels in the motor and somatosensory brain cortex of offspring (postnatal day 5) from PELS compared with uncomplicated control offspring. These data were confirmed using 2 additional PELS models. Furthermore, circulating levels of critical proangiogenic factors, VEGF (vascular endothelial growth factor), and PlGF (placental growth factor) were lower in postnatal day 5 PELS. Also we found lower VEGF receptor 2 (KDR [kinase insert domain-containing receptor]) levels in mice and human endothelial cells exposed to the serum of postnatal day 5 PELS or fetal plasma of preeclamptic pregnancies, respectively. These changes were associated with lower in vitro angiogenic capacity, diminished cell migration, larger F-actin filaments, lower number of filopodia, and lower protein levels of F-actin polymerization regulators in brain endothelial cells exposed to serum or fetal plasma of offspring from preeclampsia. CONCLUSIONS: Offspring from preeclampsia exhibited diminished brain cortex angiogenesis, associated with lower circulating VEGF/PlGF/KDR protein levels, impaired brain endothelial migration, and dysfunctional assembly of F-actin filaments. These alterations may predispose to structural and functional alterations in long-term brain development.
Assuntos
Pré-Eclâmpsia , Proteínas da Gravidez , Gravidez , Criança , Feminino , Humanos , Animais , Camundongos , Fator de Crescimento Placentário/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas da Gravidez/metabolismo , Células Endoteliais/metabolismo , Encéfalo/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio VascularRESUMO
Background: We recently reported that metformin administration has substantial effects on steroid hormone concentrations. In this study, we specifically explored which enzymatic activities were affected before a first treatment versus after a time of metformin treatment. Material and Methods: Twelve male subjects (54.2 ± 9.1 years, 177.3 ± 4.1 cm, 80 ± 10.4 kg) and seven female subjects (57.2 ± 18.9 years, 162.7 ± 4.1 cm, 76.1 ± 10.4 kg) were recruited based on an indication of metformin. Prior to the first intake of metformin and after 24 h, urine collections were performed. Urine steroid analysis was completed using gas chromatography-mass spectrometry. Results: The average reduction in steroid hormone concentrations after the metformin treatment was substantial and relatively equally distributed in all metabolites and the sum of all metabolites with 35.4%. An exception was dehydroepiandrosterone, with a decrease of almost three hundred percent of average concentration. In addition, the sum of all cortisol metabolites and 18-OH cortisol (indicative of oxidative stress) were lower after the metformin treatment. Furthermore, significant inhibition of 3ß-HSD activity was detectable. Discussion: Effects prior to and after the metformin treatment on inhibiting 3ß-HSD activity were detected in line with findings from others. Furthermore, the pattern of a reduction, for example, in the sum of all glucocorticoids following the metformin treatment supported an effect on oxidative stress, which was further supported by the reduction in 18-OH cortisol. Nevertheless, we do not understand all steps in the complex pattern of the enzymes that affect steroid hormone metabolism and, consequently, further studies are necessary to improve our understanding.
RESUMO
Trace elements such as selenium and zinc are vital components of many enzymes, including endogenous antioxidants, and can interact with each other. Women with pre-eclampsia, the hypertensive disease of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (p < 0.05), as were fetal plasma selenium and manganese (p < 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (p < 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (p < 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (p < 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (p < 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.
Assuntos
Hipertensão , Micronutrientes , Placenta , Pré-Eclâmpsia , Selênio , Oligoelementos , Feminino , Humanos , Gravidez , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Cobre , Hipertensão/complicações , Manganês , Micronutrientes/metabolismo , Micronutrientes/farmacologia , Placenta/metabolismo , Fator de Crescimento Placentário , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/urina , Oligoelementos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Zinco/metabolismoRESUMO
Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18-29, 30-39, and 40-49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Gravidez , Humanos , Feminino , Adolescente , Inglaterra/epidemiologia , Etnicidade , Reprodução , VacinaçãoRESUMO
INTRODUCTION: Endoplasmic reticulum resident protein 44 (ERp44) is a zinc-metalloprotein, regulating Endoplasmic reticulum aminopeptidase 1 (ERAP1) and Angiotensin II (Ang II). We explored placental ERp44 expression and components of the renin-angiotensin-system (RAS) in pre-eclampsia (PE), correlating these to ERAP1 expression and placental zinc concentrations. METHODS: Placental tissue, taken at time of delivery in normotensive women or women with PE (n = 12/group), were analysed for ERp44, AT1R, AT2R and AT4R by qPCR. Protein ERp44 expression was measured by immunohistochemistry and compared to previously measured ERAP1 expression. Placental zinc was measured by inductively-coupled-mass-spectrometry. RESULTS: ERp44 gene/protein expression were increased in PE (P < 0.05). AT1R expression was increased (P = 0.02) but AT4R decreased (P = 0.01) in PE, compared to normotensive controls. A positive association between ERp44 and AT2R expression was observed in all groups. ERp44 was negatively correlated with ERAP1 protein expression in all samples. Placental zinc concentrations were lower in women with PE (P = 0.001) and negatively associated with ERp44 gene expression. DISCUSSION: Increased placental ERp44 could further reduce ERAP1 release in PE, potentially preventing release of Ang IV and thus lowering levels of Ang IV which consequently diminishes the possibility of counterbalancing the activity of vasoconstrictive, Ang II. The lower placental zinc may contribute to dysfunction of the ERp44/ERAP1 complex, exacerbating the hypertension in PE.
Assuntos
Placenta , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Renina/metabolismo , Zinco/metabolismo , Angiotensina II/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/genética , Aminopeptidases/genética , Antígenos de Histocompatibilidade Menor/metabolismoRESUMO
OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs when used within pregnancy. DATA SOURCES: Electronic databases were searched (2017-2021) for measurements of blood pressure in pregnancy at >20 weeks, classified according to the 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. Blood pressure was categorized as "normal" (systolic blood pressure of <120 mm Hg and diastolic blood pressure of <80 mm Hg), "elevated blood pressure" (systolic blood pressure of 120-129 mm Hg and diastolic blood pressure of <80 mm Hg), "stage 1 hypertension" (systolic blood pressure of 130-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg), and "stage 2 hypertension" (systolic blood pressure of ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg). STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at or above 20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated accounting for gestation. RESULTS: There were 12 included studies. The American College of Cardiology or American Heart Association blood pressure categories were determined from peak blood pressures at any point from 20 weeks of gestation and at specific gestational ages (20-27, 28-32, or 33-36 weeks of gestation), as available. A higher (vs normal) blood pressure category was consistently associated with adverse outcomes. The strength of association between blood pressure categories and adverse outcomes was the greatest with "stage 2 hypertension" (blood pressure of ≥140/90 mm Hg). The results were similar when peak blood pressure was reported either at any time from 20 weeks of gestation or within gestational age groups (as above). No blood pressure category was useful as a diagnostic "rule-out test" for adverse outcomes, as all negative likelihood ratios were ≥0.2. Only "stage 2 hypertension" was useful as a "rule in-test," with positive likelihood ratios of ≥5.0, for maximum blood pressure at >20 weeks of gestation for preeclampsia and blood pressure within any gestational age groups for preeclampsia, eclampsia, stroke, maternal death, and stillbirth. CONCLUSION: From 20 weeks of gestation, blood pressure thresholds of 140 mm Hg (systolic) and 90 mm Hg (diastolic) were useful in identifying women at increased risk of adverse pregnancy outcomes, irrespective of the specific gestational age at blood pressure measurement. Lowering the blood pressure threshold for abnormal blood pressure at >20 weeks of gestation would not assist clinicians in identifying women at heightened maternal or perinatal risk. No American College of Cardiology or American Heart Association blood pressure threshold can provide reassurance that women are unlikely to develop adverse outcomes.
Assuntos
Pressão Sanguínea , Hipertensão , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , American Heart Association , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/complicações , Pré-Eclâmpsia/diagnóstico , Resultado da Gravidez , Determinação da Pressão ArterialRESUMO
OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs. DATA SOURCES: We systematically searched electronic databases (from 2017 to 2021) for reports of blood pressure measurements in pregnancy, classified according to 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at <20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated. RESULTS: Of 23 studies included, there was a stepwise relationship between the American College of Cardiology and American Heart Association blood pressure category (when compared with normal blood pressure of <120/80 mmHg) and the strength of the association with preeclampsia. The category of elevated blood pressure had a risk ratio of 2.0 (95% prediction interval, 0.8-4.8), the stage 1 hypertension category had a risk ratio of 3.0 (95% prediction interval, 1.1-8.5), and the stage 2 hypertension category had a risk ratio of 7.9 (95% prediction interval, 1.8-35.1). Between-study variability was related to the magnitude of the association with stronger relationships in larger studies at low risk of bias and with unselected populations with multiple routine blood pressure measurements. None of the systolic blood pressure measurements of <120 mmHg, <130/80 mmHg, or <140/90 mmHg were useful to rule out the development of preeclampsia (all negative likelihood ratios >0.2). Only a blood pressure measurement of ≥140/90 mmHg was a good predictor for the development of preeclampsia (positive likelihood ratio, 5.95). The findings were similar for other outcomes. CONCLUSION: Although a blood pressure of 120 to 140 over 80 to 90 mmHg at <20 weeks gestation is associated with a heightened risk for preeclampsia and adverse pregnancy outcomes and may assist in risk prediction in multivariable modelling, lowering the diagnostic threshold for chronic hypertension would not assist clinicians in identifying women at heightened risk.
Assuntos
Cardiologia , Hipertensão , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Estados Unidos/epidemiologia , Pressão Sanguínea , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Resultado da Gravidez , American Heart Association , Hipertensão/epidemiologiaRESUMO
Pre-eclampsia is a serious complication of pregnancy, and maternal nutritional factors may play protective roles or exacerbate risk. The tendency to focus on single nutrients as a risk factor obscures the complexity of possible interactions, which may be important given the complex nature of pre-eclampsia. An evidence review was conducted to compile definite, probable, possible and indirect nutritional determinants of pre-eclampsia to map a nutritional conceptual framework for pre-eclampsia prevention. Determinants of pre-eclampsia were first compiled through an initial consultation with experts. Second, an expanded literature review was conducted to confirm associations, elicit additional indicators and evaluate evidence. The strength of association was evaluated as definite relative risk (RR) < 0·40 or ≥3·00, probable RR 0·40-0·69 or 1·50-2·99, possible RR 0·70-0·89 or 1·10-1·49 or not discernible RR 0·90-1·09. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Twenty-five nutritional factors were reported in two umbrella reviews and twenty-two meta-analyses. Of these, fourteen were significantly associated with pre-eclampsia incidence. Higher serum Fe emerged as a definite nutritional risk factors for pre-eclampsia incidence across populations, while low serum Zn was a risk factor in Asia and Africa. Maternal vitamin D deficiency was a probable risk factor and Ca and/or vitamin D supplementation were probable protective nutritional factors. Healthy maternal dietary patterns were possibly associated with lower risk of developing pre-eclampsia. Potential indirect pathways of maternal nutritional factors and pre-eclampsia may exist through obesity, maternal anaemia and gestational diabetes mellitus. Research gaps remain on the influence of household capacities and socio-cultural, economic and political contexts, as well as interactions with medical conditions.
Assuntos
Diabetes Gestacional , Pré-Eclâmpsia , Deficiência de Vitamina D , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/prevenção & controle , Suplementos Nutricionais , ÁfricaRESUMO
Background: Evidence exists that steroid hormones are altered in individuals with autism, especially androgens. Despite lower prevalence in girls than boys, evidence of potential alterations in progesterone metabolites is sparse, so the aim of this study was to elucidate different progesterone metabolites in affected children with autism versus healthy controls. Material and Methods: Circadian urine samples from 48 boys and 16 girls with autism spectrum disorders and a matched case−control group were analysed for progesterone metabolites by gas chromatography−mass spectrometry and normalised for creatinine excretion. Results: In boys with autism, the majority of progesterone metabolites were reduced, such as progesterone, 6a-OH-3a5b-TH-progesterone, or 20a-DH-progesterone (p < 0.01 for all). In girls with autism, a similar pattern of reduction in progesterone metabolites was detected; however, potentially due to the relatively small sample, this pattern was only detectable on the level of a trend. Discussion: As stated, androgen levels are higher in boys and girls with autism, but evidence for progesterone metabolites is much sparser. The pattern of a decrease in progesterone metabolites suggests the existence of an altered routing of steroid metabolites, probably in combination with a dysregulation of the HPAG axis. As, recently, increased CYP17A1 activity has been suggested, the stronger routing towards androgens is further implied in line with our findings of lower progesterone concentrations in boys and girls with autism than healthy controls.
RESUMO
Preeclampsia (PE) is a pregnancy-specific disorder that affects 3 to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Nevertheless, how these events occur remains unclear. We hypothesized that the induction of hypoxic conditions in vitro in primary human trophoblast cells would mimic several characteristics of PE found in vivo. We applied and characterized a model of primary cytotrophoblasts isolated from healthy pregnancies that were placed under different oxygen concentrations: ambient O2 (5% pCO2, 21%pO2, 24 h, termed "normoxia"), low O2 concentration (5% pCO2, 1.5% pO2, 24 h, termed "hypoxia"), or "hypoxia/reoxygenation" (H/R: 6 h intervals of normoxia and hypoxia for 24 h). Various established preeclamptic markers were assessed in this cell model and compared to placental tissues obtained from PE pregnancies. Seventeen PE markers were analyzed by qPCR, and the protein secretion of soluble fms-like tyrosine kinase 1 (sFlT-1) and the placenta growth factor (PlGF) was determined by ELISA. Thirteen of seventeen genes associated with angiogenesis, the renin-angiotensin system, oxidative stress, endoplasmic reticulum stress, and the inflammasome complex were susceptible to H/R and hypoxia, mimicking the expression pattern of PE tissue. In cell culture supernatants, the secretion of sFlT-1 was increased in hypoxia, while PlGF release was significantly reduced in H/R and hypoxia. In the supernatants of our cell models, the sFlT-1/PlGF ratio in hypoxia and H/R was higher than 38, which is a strong indicator for PE in clinical practice. These results suggest that our cellular models reflect important pathological processes occurring in PE and are therefore suitable as PE in vitro models.