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Hypertension in Pregnancy Dec 2024Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality... (Review)
Review
Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Genetic Therapy; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38817101
DOI: 10.1080/10641955.2024.2358761 -
Nutrition & Diabetes May 2024Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
BACKGROUND
Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
OBJECTIVE
To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes.
METHODS
Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted.
DATA EXTRACTION
Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2).
RESULTS
We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization.
CONCLUSION
Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.
Topics: Humans; Pregnancy; Female; Vitamin D Deficiency; Vitamin D; Pregnancy Complications; Dietary Supplements; Pregnancy Outcome; Systematic Reviews as Topic; Meta-Analysis as Topic; Infant, Newborn; Premature Birth
PubMed: 38816412
DOI: 10.1038/s41387-024-00296-0 -
PloS One 2024Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental...
BACKGROUND AND AIM
Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women.
METHODS
This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant.
RESULTS
Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584-6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055-0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE.
CONCLUSION
This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE.
Topics: Humans; Female; Receptors, Calcitriol; Pre-Eclampsia; Pregnancy; Ghana; Adult; Case-Control Studies; Vitamin D; Genetic Predisposition to Disease; Genotype; Vitamin D Deficiency; Polymorphism, Single Nucleotide; Young Adult; Risk Factors
PubMed: 38814968
DOI: 10.1371/journal.pone.0303778 -
JAMA Network Open May 2024
Topics: Humans; Female; Pregnancy; Dementia; Pre-Eclampsia; Adult; Risk Factors; Age of Onset; Male
PubMed: 38814648
DOI: 10.1001/jamanetworkopen.2024.12780 -
JAMA Network Open May 2024
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Dementia; Adult; Age of Onset; Male; Middle Aged
PubMed: 38814647
DOI: 10.1001/jamanetworkopen.2024.12870 -
Turkish Journal of Medical Sciences 2023This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and...
BACKGROUND/AIM
This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and magnesium sulfate (MgSO) used separately and together on feto-maternal outcomes.
MATERIALS AND METHODS
We created PE in rats using a reduced uterine perfusion pressure (RUPP) animal model and recorded blood pressure (BP), embryonic survival (ES), and embryonic weight (EW) and evaluated cochlear morphology by electron microscopy.
RESULTS
The PE group had elevated BP, a decreased number and weight of live pups, and significant degeneration in the cochlea compared to the sham group. In the PEV group, we observed significant beneficial effects of Vit D supplementation at 14.5 and 19.5 dpc in terms of BP (p < 0.05), EW (p < 0.001), and cochlear degeneration compared to the PE group. In the PEM group, BP (p < 0.05) and cochlear degeneration nearly reached the level found in the sham group. However, although the EW was statistically different in the PE group, it did not reach sham group levels. We also observed that BP returned to sham level (p < 0.01) and noticed significant increases in the EW (p < 0.0001) and ES (p = 0.017) in the PEMV group compared to the PE group. According to the scanning electron microscope results, combined administration of VitD and MgSO is more effective than separate administration in improving cochlear degeneration induced by PE.
CONCLUSION
The administration of Vit D and MgSO during pregnancy has beneficial effects on PE pathology and may play a significant role in preventing PE-related complications, including cochlear degeneration.
Topics: Animals; Magnesium Sulfate; Pre-Eclampsia; Female; Pregnancy; Cochlea; Vitamin D; Rats; Disease Models, Animal; Rats, Sprague-Dawley
PubMed: 38813514
DOI: 10.55730/1300-0144.5730 -
EClinicalMedicine May 2024Spontaneous and induced abortions are common outcomes of pregnancy. There is inconsistent evidence of an association between early pregnancy loss and subsequent diabetic... (Review)
Review
BACKGROUND
Spontaneous and induced abortions are common outcomes of pregnancy. There is inconsistent evidence of an association between early pregnancy loss and subsequent diabetic and hypertensive disorders in women. This systematic review and meta-analysis evaluated evidence on the risk of the subsequent development of pregnancy and non-pregnancy related diabetic and hypertensive disorders in women who experienced an early pregnancy loss.
METHODS
Systematic searches were conducted in seven electronic databases (CINAHL Plus, Ovid/EMBASE, Ovid/MEDLINE, ProQuest, PubMed, Scopus, and Web of Science) from inception to 22nd December 2023. Studies were included if they reported an exposure of spontaneous abortion (SAB), induced abortion (IA) or recurrent pregnancy loss (RPL) with an outcome of gestational diabetes mellitus, pre-eclampsia, gestational hypertension, and non-pregnancy related diabetic and hypertensive disorders. Risk of bias was assessed using Risk of Bias Instrument for Non-Randomized Studies of Exposures (ROBINS-E). Random effects meta-analysis was used to pool odds of developing diabetic and hypertensive disorders following an early pregnancy loss. This study is registered with PROSPERO (CRD42022327689).
FINDINGS
Of 20,176 records, 60 unique articles were identified for full-text review and 52 met the inclusion criteria, representing a total population of 4,132,895 women from 22 countries. Thirty-five studies were suitable for meta-analysis, resulting in a pooled odds ratio (OR) of 1.44 (95% confidence interval (CI) 1.23-1.68) for gestational diabetes mellitus following a prior SAB and a pooled OR of 1.06 (95% CI 0.90-1.26) for pre-eclampsia following a prior SAB. RPL increased the odds of developing pre-eclampsia (OR 1.37 95% CI 1.05-1.79). There was no association between IA and diabetic and hypertensive disorders.
INTERPRETATION
A prior SAB was associated with increased odds of gestational diabetes mellitus, but not pre-eclampsia. However, women who experienced RPL had an increased risk of subsequent pre-eclampsia. Future research is required to establish evidence for an association between early pregnancy loss with non-pregnancy related diabetic and hypertensive disorders.
FUNDING
National Health and Medical Research Council.
PubMed: 38813443
DOI: 10.1016/j.eclinm.2024.102560 -
Current Hypertension Reports Jul 2024Machine learning (ML) approaches are an emerging alternative for healthcare risk prediction. We aimed to synthesise the literature on ML and classical regression studies... (Review)
Review
PURPOSE OF REVIEW
Machine learning (ML) approaches are an emerging alternative for healthcare risk prediction. We aimed to synthesise the literature on ML and classical regression studies exploring potential prognostic factors and to compare prediction performance for pre-eclampsia.
RECENT FINDINGS
From 9382 studies retrieved, 82 were included. Sixty-six publications exclusively reported eighty-four classical regression models to predict variable timing of onset of pre-eclampsia. Another six publications reported purely ML algorithms, whilst another 10 publications reported ML algorithms and classical regression models in the same sample with 8 of 10 findings that ML algorithms outperformed classical regression models. The most frequent prognostic factors were age, pre-pregnancy body mass index, chronic medical conditions, parity, prior history of pre-eclampsia, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and pregnancy-associated plasma protein A. Top performing ML algorithms were random forest (area under the curve (AUC) = 0.94, 95% confidence interval (CI) 0.91-0.96) and extreme gradient boosting (AUC = 0.92, 95% CI 0.90-0.94). The competing risk model had similar performance (AUC = 0.92, 95% CI 0.91-0.92) compared with a neural network. Calibration performance was not reported in the majority of publications. ML algorithms had better performance compared to classical regression models in pre-eclampsia prediction. Random forest and boosting-type algorithms had the best prediction performance. Further research should focus on comparing ML algorithms to classical regression models using the same samples and evaluation metrics to gain insight into their performance. External validation of ML algorithms is warranted to gain insights into their generalisability.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Machine Learning; Algorithms; Prognosis; Regression Analysis; Risk Assessment; Risk Factors; Predictive Value of Tests
PubMed: 38806766
DOI: 10.1007/s11906-024-01297-1 -
Medical Ultrasonography Jun 2024Accurate prediction of preeclampsia could improve maternal outcomes. However, the role of uterine artery Doppler ultrasound in predicting preeclampsia remains unclear. (Meta-Analysis)
Meta-Analysis Review
AIMS
Accurate prediction of preeclampsia could improve maternal outcomes. However, the role of uterine artery Doppler ultrasound in predicting preeclampsia remains unclear.
MATERIALS AND METHODS
We comprehensively searched several electronic databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science, covering studies published from the time of database creation to September 23, 2023. Studies on the predictive value of uterine artery Doppler ultrasound for preeclampsia were included. The primary pregnancy outcome was preeclampsia. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scoring scale.
RESULTS
The use of resistance index (RI) for predicting preeclampsia demonstrated the highest sensitivity of 0.73 (95% confidence interval [CI], 0.30-0.94) and specificity of 0.90 (95% CI, 0.72-0.97), with a pooled area under the curve value of 0.91 (95% CI, 0.88-0.93). The use of pulsatility index (PI) for predicting preeclampsia showed a sensitivity of 0.65 (95% CI, 0.45-0.81) and specificity of 0.88 (95% CI, 0.77-0.94). Furthermore, preeclampsia prediction via notching showed a sensitivity of 0.54 (95% CI, 0.38-0.68) and specificity of 0.89 (95% CI, 0.79-0.95).
CONCLUSIONS
These findings highlight the varying predictive performance of different preeclampsia indices. PI and RI demonstrated moderate-to-high sensitivity and specificity, whereas notching exhibited relatively lower sensitivity but comparable specificity. Further research and validation are warranted to consolidate these results and enhance the accuracy of preeclampsia prediction.
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Uterine Artery; Ultrasonography, Doppler; Sensitivity and Specificity; Predictive Value of Tests; Ultrasonography, Prenatal
PubMed: 38805623
DOI: 10.11152/mu-4355 -
Neurology International May 2024Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes... (Review)
Review
Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes the current evidence on the epidemiology, pathophysiology, and neurological consequences of OSA in pregnancy, along with the potential management strategies. Articles were sourced from the PubMed, EMBASE, and Cochrane databases until 2023. Our comprehensive review highlights that the incidence of OSA increases during pregnancy due to physiological changes such as weight gain and hormonal fluctuations. OSA in pregnancy is linked with gestational hypertension, pre-eclampsia, gestational diabetes, and potential adverse fetal outcomes such as intrauterine growth restriction and preterm birth. Continuous positive airway pressure (CPAP) therapy remains the most effective management strategy for pregnant women with OSA. However, adherence to CPAP therapy is often suboptimal. This comprehensive review underscores the importance of the early recognition, timely diagnosis, and effective management of OSA in pregnancy to improve both maternal and fetal outcomes. Future research should focus on enhancing screening strategies and improving adherence to CPAP therapy in this population.
PubMed: 38804478
DOI: 10.3390/neurolint16030039