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Molecular Medicine (Cambridge, Mass.) Jul 2023Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in...
BACKGROUND
Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition.
METHODS
The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition.
RESULTS
Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice.
CONCLUSION
IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.
Topics: Animals; Female; Humans; Infant, Newborn; Mice; Pregnancy; Amnion; Fibroblasts; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; NF-kappa B; Parturition; Premature Birth
PubMed: 37403020
DOI: 10.1186/s10020-023-00668-9 -
Cureus Nov 2023Many researchers have reported on the high prevalence of anxiety and depression during pregnancy as well as the influence on delivery outcomes during the past decade.... (Review)
Review
Many researchers have reported on the high prevalence of anxiety and depression during pregnancy as well as the influence on delivery outcomes during the past decade. Preterm birth and premature labor, bleeding, higher frequency of cesarean section (CS), low birth weight, preeclampsia, stillbirth, miscarriage, NICU hospitalization, and a low Apgar score are the most commonly referenced outcomes assessed. Clarifying the relationship between exposure and result may help us to understand the risk factors and guide us to future clinical and research practices. The purpose of this narrative review is to search the following databases: PubMed, Research Gate, Scopus, Medline Plus, and present the most recent, comprehensive literature on the effects of stress and anxiety on pregnancy outcomes. Articles published from 01/01/2000 to 26/11/2022 were obtained from the previous databases. Anxiety and depression-related disorders are common nowadays, and they are frequently correlated with poor pregnancy outcomes. These problems are caused by a number of factors, including health social determinants, the individual obstetric situation, access to healthcare facilities, etc. The effects of each of these factors on birth outcomes range from major, such as preterm labor, congenital deformities, and low birth weight, to minor, such as mutations in the fetal epigenome. Both direct and indirect pathways of substantial interactions between depression, anxiety and stress, risk variables, and delivery problems were identified. Women's health practitioners and mental physicians must provide adequate support to these women in order to improve outcomes for both mothers and infants.
PubMed: 38090445
DOI: 10.7759/cureus.48700 -
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 -
ELife Aug 2023Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific...
Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. We report findings stemming from unbiased transcriptomic analysis of mouse placenta, which revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysregulation and cellular senescence; we detected similar effects in aging human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma cells, we modeled HIF-1 induction and demonstrated resultant mitochondrial dysfunction and cellular senescence. Transcriptomic analysis revealed that HIF-1 stabilization recapitulated gene signatures observed in aged placenta. Further, conditioned media from trophoblasts following HIF-1 induction promoted contractility in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may drive the transition from uterine quiescence to contractility at the onset of labor. Finally, pharmacological induction of HIF-1 via intraperitoneal administration of dimethyloxalyl glycine (DMOG) to pregnant mice caused preterm labor. These results provide clear evidence for placental aging in normal pregnancy, and demonstrate how HIF-1 signaling in late gestation may be a causal determinant of the mitochondrial dysfunction and senescence observed within the trophoblast as well as a trigger for uterine contraction.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Animals; Mice; Aged; Placenta; Premature Birth; Obstetric Labor, Premature; Aging; Hypoxia-Inducible Factor 1
PubMed: 37610425
DOI: 10.7554/eLife.85597 -
Obstetrics and Gynecology Dec 2023To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous...
OBJECTIVE
To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous physical activity, healthy eating [top 40% of Dietary Approaches to Stop Hypertension score], no or low-to-moderate alcohol intake [less than 15 g/d], and use of multivitamins) with risk of adverse pregnancy outcomes.
METHODS
We conducted a secondary analysis of prospectively collected data for women without chronic diseases who are participating in an ongoing cohort in the United States (the NHSII [Nurses' Health Study II]). Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2-4 years from 1991 to 2009 with validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of adverse pregnancy outcomes that included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, or low birth weight was assessed.
RESULTS
Overall, 15,509 women with 27,135 pregnancies were included. The mean maternal age was 35.1±4.2 years. Approximately one in three pregnancies (n=9,702, 35.8%) was complicated by one or more adverse pregnancy outcomes. The combination of six low-risk factors was inversely associated with risk of adverse pregnancy outcomes in a dose-dependent manner ( P for trend <.001). Compared with women who had zero or one healthy lifestyle factor, those with six had a 37% lower risk of adverse pregnancy outcomes (relative risk 0.63, 95% CI 0.55-0.72), driven primarily by lower risks of gestational diabetes, gestational hypertension, and low birth weight. All prepregnancy healthy lifestyle factors, except avoiding harmful alcohol consumption and regular physical activity, were independently associated with lower risk of adverse pregnancy outcomes after mutual adjustment for each other. Healthy BMI, high-quality diet, and multivitamin supplementation showed the strongest inverse associations with adverse pregnancy outcomes. If the observed relationships were causal, 19% of adverse pregnancy outcomes could have been prevented by the adoption of all six healthy lifestyle factors (population attributable risk 19%, 95% CI 13-26%).
CONCLUSION
Prepregnancy healthy lifestyle is associated with a substantially lower risk of adverse pregnancy outcomes and could be an effective intervention for the prevention of adverse pregnancy outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Adult; Pregnancy Outcome; Diabetes, Gestational; Hypertension, Pregnancy-Induced; Premature Birth; Risk Factors; Healthy Lifestyle
PubMed: 37826849
DOI: 10.1097/AOG.0000000000005346 -
American Journal of Obstetrics &... May 2024
Topics: Female; Humans; Cervix Uteri; Premature Birth
PubMed: 38582652
DOI: 10.1016/j.ajogmf.2024.101347 -
Best Practice & Research. Clinical... Aug 2023A number of reproductive outcomes have been increasingly found to be affected by the vaginal microbiota. Obesity has become a global epidemic, affecting increasing... (Review)
Review
A number of reproductive outcomes have been increasingly found to be affected by the vaginal microbiota. Obesity has become a global epidemic, affecting increasing numbers of reproductive-age women, and has been shown to be a risk factor for a number of adverse female health outcomes. A healthy vaginal microbiome is characterized by Lactobacillus-dominance, in particular Lactobacillus crispatus; obesity has been found to be associated with higher diversity and a lower likelihood of Lactobacillus-dominance. In this review, we summarize the evidence on the vaginal microbiome in obese women and the impact on reproductive outcomes such as conception rates, early pregnancy, and preterm birth. We further explore the mechanisms by which obesity may result in an altered microbial composition and highlight future avenues for therapeutic targeting of the vaginal microbiota.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Reproduction; Vagina; Obesity; Microbiota
PubMed: 37399714
DOI: 10.1016/j.bpobgyn.2023.102365 -
Biology of Reproduction Sep 2023During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports... (Review)
Review
During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its "bright side" during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this "dark side" promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta; Premature Birth; Parturition; Placentation; Cellular Senescence
PubMed: 37402700
DOI: 10.1093/biolre/ioad071 -
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 -
The Journal of Maternal-fetal &... Dec 2023This meta-analysis aimed to investigate the relationship between hyperuricemia and maternal and neonatal complications in pregnant women. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This meta-analysis aimed to investigate the relationship between hyperuricemia and maternal and neonatal complications in pregnant women.
METHODS
We searched PubMed, Embase, Web of Science, and the Cochrane Library from the databases' inception to August 12, 2022. We included studies that reported results on the association between hyperuricemia and maternal and fetal outcomes among pregnant women. Using the random-effects model, the pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated for each outcome analysis.
RESULTS
A total of 7 studies, including 8104 participants, were included. The pooled OR for pregnancy-induced hypertension (PIH) was 2.61 [0.26, 26.56] ( = 0.81, = .4165; = 96.3%). The pooled OR for preterm birth was 2.52 [1.92, 3.30] ( = 6.64, < .0001; = 0%). The pooled OR for low birth weight (LBW) was 3.44 [2.52, 4.70] ( = 7.77, < .0001; = 0%). The pooled OR for small gestational age (SGA) was 1.81 [0.60, 5.46] ( = 1.06, = .2912; = 88.6%).
CONCLUSION
Results of this meta-analysis indicate a positive relationship between hyperuricemia and PIH, preterm birth, LBW, and SGA in pregnant women.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pregnancy Outcome; Premature Birth; Pregnant Women; Hyperuricemia; Prenatal Care; Hypertension, Pregnancy-Induced
PubMed: 37193631
DOI: 10.1080/14767058.2023.2212830