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The Cochrane Database of Systematic... Aug 2022Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type... (Review)
Review
BACKGROUND
Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type of corticosteroid to use, dose, frequency, timing of use or the route of administration. OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal morbidity and mortality, and on the child and adult in later life, of administering different types of corticosteroids (dexamethasone or betamethasone), or different corticosteroid dose regimens, including timing, frequency and mode of administration.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 May 2022) and reference lists of retrieved studies.
SELECTION CRITERIA
We included all identified published and unpublished randomised controlled trials or quasi-randomised controlled trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth. We planned to exclude cross-over trials and cluster-randomised trials. We planned to include studies published as abstracts only along with studies published as full-text manuscripts.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 11 trials (2494 women and 2762 infants) in this update, all of which recruited women who were at increased risk of preterm birth or had a medical indication for preterm birth. All trials were conducted in high-income countries. Dexamethasone versus betamethasone Nine trials (2096 women and 2319 infants) compared dexamethasone versus betamethasone. All trials administered both drugs intramuscularly, and the total dose in the course was consistent (22.8 mg or 24 mg), but the regimen varied. We assessed one new study to have no serious risk of bias concerns for most outcomes, but other studies were at moderate (six trials) or high (two trials) risk of bias due to selection, detection and attrition bias. Our GRADE assessments ranged between high- and low-certainty, with downgrades due to risk of bias and imprecision. Maternal outcomes The only maternal primary outcome reported was chorioamnionitis (death and puerperal sepsis were not reported). Although the rate of chorioamnionitis was lower with dexamethasone, we did not find conclusive evidence of a difference between the two drugs (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.48 to 1.06; 1 trial, 1346 women; moderate-certainty evidence). The proportion of women experiencing maternal adverse effects of therapy was lower with dexamethasone; however, there was not conclusive evidence of a difference between interventions (RR 0.63, 95% CI 0.35 to 1.13; 2 trials, 1705 women; moderate-certainty evidence). Infant outcomes We are unsure whether the choice of drug makes a difference to the risk of any known death after randomisation, because the 95% CI was compatible with both appreciable benefit and harm with dexamethasone (RR 1.03, 95% CI 0.66 to 1.63; 5 trials, 2105 infants; moderate-certainty evidence). The choice of drug may make little or no difference to the risk of RDS (RR 1.06, 95% CI 0.91 to 1.22; 5 trials, 2105 infants; high-certainty evidence). While there may be little or no difference in the risk of intraventricular haemorrhage (IVH), there was substantial unexplained statistical heterogeneity in this result (average (a) RR 0.71, 95% CI 0.28 to 1.81; 4 trials, 1902 infants; I² = 62%; low-certainty evidence). We found no evidence of a difference between the two drugs for chronic lung disease (RR 0.92, 95% CI 0.64 to 1.34; 1 trial, 1509 infants; moderate-certainty evidence), and we are unsure of the effects on necrotising enterocolitis, because there were few events in the studies reporting this outcome (RR 5.08, 95% CI 0.25 to 105.15; 2 studies, 441 infants; low-certainty evidence). Longer-term child outcomes Only one trial consistently followed up children longer term, reporting at two years' adjusted age. There is probably little or no difference between dexamethasone and betamethasone in the risk of neurodevelopmental disability at follow-up (RR 1.02, 95% CI 0.85 to 1.22; 2 trials, 1151 infants; moderate-certainty evidence). It is unclear whether the choice of drug makes a difference to the risk of visual impairment (RR 0.33, 95% CI 0.01 to 8.15; 1 trial, 1227 children; low-certainty evidence). There may be little or no difference between the drugs for hearing impairment (RR 1.16, 95% CI 0.63 to 2.16; 1 trial, 1227 children; moderate-certainty evidence), motor developmental delay (RR 0.89, 95% CI 0.66 to 1.20; 1 trial, 1166 children; moderate-certainty evidence) or intellectual impairment (RR 0.97, 95% CI 0.79 to 1.20; 1 trial, 1161 children; moderate-certainty evidence). However, the effect estimate for cerebral palsy is compatible with both an important increase in risk with dexamethasone, and no difference between interventions (RR 2.50, 95% CI 0.97 to 6.39; 1 trial, 1223 children; low-certainty evidence). No trials followed the children beyond early childhood. Comparisons of different preparations and regimens of corticosteroids We found three studies that included a comparison of a different regimen or preparation of either dexamethasone or betamethasone (oral dexamethasone 32 mg versus intramuscular dexamethasone 24 mg; betamethasone acetate plus phosphate versus betamethasone phosphate; 12-hourly betamethasone versus 24-hourly betamethasone). The certainty of the evidence for the main outcomes from all three studies was very low, due to small sample size and risk of bias. Therefore, we were limited in our ability to draw conclusions from any of these studies.
AUTHORS' CONCLUSIONS
Overall, it remains unclear whether there are important differences between dexamethasone and betamethasone, or between one regimen and another. Most trials compared dexamethasone versus betamethasone. While for most infant and early childhood outcomes there may be no difference between these drugs, for several important outcomes for the mother, infant and child the evidence was inconclusive and did not rule out significant benefits or harms. The evidence on different antenatal corticosteroid regimens was sparse, and does not support the use of one particular corticosteroid regimen over another.
Topics: Adrenal Cortex Hormones; Betamethasone; Child; Child, Preschool; Chorioamnionitis; Dexamethasone; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Lung; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn
PubMed: 35943347
DOI: 10.1002/14651858.CD006764.pub4 -
American Journal of Obstetrics &... Jun 2023This study aimed to determine whether cervical cerclage for a transvaginal ultrasound-detected short cervical length after 24 weeks of gestation in singleton pregnancies... (Meta-Analysis)
Meta-Analysis Review
Cervical cerclage for short cervix at 24 to 26 weeks of gestation: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.
OBJECTIVE
This study aimed to determine whether cervical cerclage for a transvaginal ultrasound-detected short cervical length after 24 weeks of gestation in singleton pregnancies reduces the risk for preterm birth.
DATA SOURCES
Ovid MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched using the following terms: "cerclage, cervical," "uterine cervical incompetence," "obstetrical surgical procedures," "cervix uteri," "randomized controlled trial," and "controlled clinical trial."
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials comparing cerclage placement with no cerclage in singleton gestations with a transvaginal ultrasound-detected short cervical length ≤25 mm between 24+0/7 and 29+6/7 weeks of gestation were eligible for inclusion.
METHODS
Individual patient-level data from each trial were collected. If an eligible trial included patients with both multiple and singleton gestations with a short cervical length detected either before or after 24+0/7 weeks of gestation, only singletons who presented at or after 24+0/7 weeks were included. The primary outcome was preterm birth <37 weeks' gestation. Secondary outcomes included preterm birth <34, <32, and <28 weeks' gestation, gestational age at delivery, latency, preterm prelabor rupture of membranes, chorioamnionitis, and adverse neonatal outcomes. Individual patient-level data from each trial were analyzed using a 2-stage approach. Pooled relative risks or mean differences with 95% confidence intervals were calculated as appropriate.
RESULTS
Data from the 4 eligible randomized controlled trials were included. A total of 131 singletons presented at 24+0/7 to 26+6/7 weeks of gestation and were further analyzed; there were no data on patients with a cerclage at 27+0/7 weeks' gestation or later. Of those included, 66 (50.4%) were in the cerclage group and 65 (49.6%) were in the no cerclage group. The rate of preterm birth <37 weeks' gestation was similar between patients who were randomized to the cerclage group and those who were randomized to the no cerclage group (27.3% vs 38.5%; relative risk, 0.78; 95% confidence interval, 0.37-1.28). Secondary outcomes including preterm birth <34, <32, and <28 weeks' gestation, gestational age at delivery, time interval from randomization to delivery, preterm prelabor rupture of membranes, and adverse neonatal outcomes such as low birthweight, very low birthweight, and perinatal death were similar between the 2 groups. Planned subgroup analyses revealed no statistically significant differences in the rate of preterm birth <37 weeks' gestation between the 2 groups when compared based on cervical length measurement (≤15 mm or ≤10 mm), gestational age at randomization (24+0/7 to 24+6/7 weeks or 25+0/7 to 26+6/7 weeks), or history of preterm birth.
CONCLUSION
Cervical cerclage did not reduce or increase the rate of preterm birth among singleton pregnancies with a short cervical length detected after 24 weeks of gestation. Because there was a 22% nonsignificant decrease in preterm birth associated with cerclage, which is a similar amount of risk reduction often associated with ultrasound-indicated cerclage before 24 weeks' gestation, further randomized controlled trials in this patient population are warranted.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Cerclage, Cervical; Premature Birth; Cervix Uteri; Randomized Controlled Trials as Topic; Gestational Age
PubMed: 36924844
DOI: 10.1016/j.ajogmf.2023.100930 -
Revista Brasileira de Ginecologia E... Aug 2023To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To perform a systematic review and meta-analysis of studies on maternal, fetal, and neonatal outcomes of women with singleton pregnancies, after spontaneous conception, and with the diagnosis of amniotic sludge before 37 weeks of gestational age.
DATA SOURCES
We conducted a search on the PubMed, Cochrane, Bireme, and Theses databases until June 2022.
SELECTION OF STUDIES
Using the keywords or or , we found 263 articles, 132 of which were duplicates, and 70 were discarded because they did not meet the inclusion criteria.
DATA COLLECTION
The articles retrieved were analyzed by 2 reviewers; 61 were selected for full-text analysis, 18 were included for a qualitative analysis, and 14, for a quantitative analysis.
DATA SYNTHESIS
Among the maternal outcomes analyzed, there was an increased risk of preterm labor (95% confidence interval [95%CI]: 1.45-2.03), premature rupture of ovular membranes (95%CI: 1.99-3.79), and clinical (95%CI: 1.41-6.19) and histological chorioamnionitis (95%CI: 1.75-3.12). Regarding the fetal outcomes, there was a significant increase in the risk of morbidity (95%CI: 1.80-3.17), mortality (95%CI: 1.14-18.57), admission to the Neonatal Intensive Care Unit (NICU; 95%CI: 1.17-1.95), and neonatal sepsis (95%CI: 2.29-7.55).
CONCLUSION
The results of the present study indicate that the presence of amniotic sludge is a risk marker for preterm delivery. Despite the heterogeneity of the studies analyzed, even in patients with other risk factors for prematurity, such as short cervix and previous preterm delivery, the presence of amniotic sludge increases the risk of premature labor. Moreover, antibiotic therapy seems to be a treatment for amniotic sludge, and it may prolong pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Premature Birth; Sewage; Gestational Age; Risk Factors; Databases, Factual
PubMed: 37683661
DOI: 10.1055/s-0043-1772189 -
CMAJ : Canadian Medical Association... May 2021
Meta-Analysis
Topics: COVID-19; Diabetes, Gestational; Female; Humans; Incidence; Infant, Low Birth Weight; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Severity of Illness Index; Stillbirth
PubMed: 34059502
DOI: 10.1503/cmaj.202604-f -
Pituitary Jun 2022To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes.
METHODS
This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17.
RESULTS
Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%).
CONCLUSION
Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.
Topics: Abortion, Spontaneous; Acromegaly; Diabetes, Gestational; Eclampsia; Female; Humans; Hypertension; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 35098440
DOI: 10.1007/s11102-022-01208-0 -
Ceska Gynekologie 2021To provide a comprehensive overview of the available information on the maternal microbio-me and its effect on pregnancy and preterm birth.
OBJECTIVE
To provide a comprehensive overview of the available information on the maternal microbio-me and its effect on pregnancy and preterm birth.
METHODS
Systematic review of available literature on the topic was done using the PubMed database.
CONCLUSION
Etiology of preterm labor is multifactorial. Individual setting of humoral and cellular immune response is key; however, lately the focus has shifted to the role of the microbio-me, especially the vaginal one. The role of additional microbio-mes and the relationship between different compartments are the focus of intensive research. Mainly the differences in the maternal and neonatal microbio-me depend on the method of delivery and administration of different antibio-tics during pregnancy and labor. The uterine cavity is no longer thought to be without colonization and the formation of the fetal microbio-me begins early in pregnancy.
Topics: Amniotic Fluid; Female; Humans; Infant, Newborn; Labor, Obstetric; Microbiota; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 35038883
DOI: 10.48095/cccg2021422 -
Ultrasound in Obstetrics & Gynecology :... Dec 2022Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may be associated with cardiac defects and tachyarrhythmia. We aimed to determine the incidence of congenital heart defects (CHDs) and complications in fetuses with PAC.
METHODS
This was a systematic review and meta-analysis conducted in accordance with the PRISMA statement for reporting items for systematic reviews and meta-analyses. MEDLINE and EMBASE were searched from 1990 to June 2021 to identify studies on fetuses with PAC. The primary outcome was CHD; secondary outcomes were complications using the endpoints supraventricular tachyarrhythmia (SVT), cardiac failure and intrauterine fetal demise. Meta-analysis of proportions was performed, subdivided into high-risk and low-risk populations based on reason for referral. Pooled incidences with 95% CIs were calculated.
RESULTS
Of 2443 unique articles identified, 19 cohort studies including 2260 fetuses were included. The pooled incidence of CHD in fetuses with PAC was 2.8% (95% CI, 1.5-4.1%), when 0.6% is the incidence expected in the general population. The pooled incidence of CHD was 7.2% (95% CI, 3.5-10.9%) in the high-risk population and 0.9% (95% CI, 0.0-2.0%) in the low-risk population. SVT occurred in 1.4% (95% CI, 0.6-3.4%) of fetuses diagnosed with PAC. Cardiac failure was described in 16 fetuses (1.4% (95% CI, 0.5-3.5%)), of which eight were CHD-related. Intrauterine fetal demise occurred in four fetuses (0.9% (95% CI, 0.5-1.7%)) and was related to CHD in two cases.
CONCLUSIONS
Our findings suggest that the risk of CHD in fetuses with PAC is 4-5 times higher than that in the general population. CHD was present more frequently in the high-risk population. Consequently, an advanced ultrasound examination to diagnose PAC correctly and exclude CHD is recommended. Complications of PAC are rare but can result in fetal demise, thus weekly fetal heart-rate monitoring remains advisable to enable early detection of SVT and to prevent cardiac failure. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Fetal Diseases; Premature Birth; Fetal Death; Atrial Premature Complexes; Fetus; Tachycardia; Arrhythmias, Cardiac; Heart Failure
PubMed: 35763619
DOI: 10.1002/uog.26017 -
PLoS Medicine Dec 2019There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes.
METHODS AND FINDINGS
CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only.
CONCLUSIONS
Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.
Topics: Case-Control Studies; Eclampsia; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Parturition; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Prospective Studies
PubMed: 31809499
DOI: 10.1371/journal.pmed.1002988 -
Reproductive Sciences (Thousand Oaks,... Jan 2022The objective of this study is to verify the association between endometriosis and preterm birth through systematic review and meta-analysis. Is there an increased risk... (Meta-Analysis)
Meta-Analysis
The objective of this study is to verify the association between endometriosis and preterm birth through systematic review and meta-analysis. Is there an increased risk of premature birth in women with endometriosis compared to women without this diagnosis? The databases searched were PubMed, Medline, and LILACS in order to identify all studies published up to April 2020, using the keywords (prematurity OR preterm birth OR premature birth OR premature labor OR obstetric premature labor OR preterm labor OR premature obstetric labor) AND (endometriosis OR adenomyosis OR endometrioma OR endometriomas). A manual research was also performed through the analysis of theses, book chapters, reference references, guidelines, and reviews. All published prospective cohort studies that reported the prevalence of preterm delivery among women with endometriosis, adenomyosis, or endometrioma were included, comparing it to the control group of women without such diagnoses. The random-effects model, the calculation of relative risk, and the confidence interval of 95% were used to perform the meta-analysis. Three studies involving 10,111 patients were included. Compared to women without endometriosis, women with endometriosis present an increased risk of premature birth (RR: 2.68, 95% CI [1.19; 6.02], I = 91%). In the subgroup of women with spontaneous conception, endometriosis is also a risk factor for prematurity (RR: 3.26, 95% CI [2.09; 5.09], I = 0%, 2 studies, 682 participants). The evidence presented suggests that women with endometriosis should be alerted to a potential risk of preterm birth. PROSPERO registration number, CRD42020189451.
Topics: Endometriosis; Female; Humans; Infant, Newborn; Pregnancy; Premature Birth
PubMed: 34426947
DOI: 10.1007/s43032-021-00712-1 -
International Journal of Molecular... Mar 2024This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial... (Review)
Review
This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial pregnancy complication. Covering studies disseminated from 2018 to 2023, the review integrates discoveries from diverse pregnancy-related scenarios, encompassing gestational diabetes, hypertensive disorders and pregnancy loss. Through meticulous search strategies and rigorous quality assessments, 47 relevant studies were incorporated. The synthesis highlights the transformative potential of microRNAs as valuable diagnostic tools, offering promising avenues for early intervention. Notably, specific miRNAs demonstrate robust predictive capabilities. In conclusion, this comprehensive analysis lays the foundation for subsequent research, intervention strategies and improved outcomes in the realm of preterm labor.
Topics: Female; Pregnancy; Infant, Newborn; Humans; Obstetric Labor, Premature; Abortion, Spontaneous; Diabetes, Gestational; Hypertension
PubMed: 38612564
DOI: 10.3390/ijms25073755