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BMC Medicine Dec 2023Preterm birth defined as delivery before 37 gestational weeks is a leading cause of neonatal and infant morbidity and mortality. The aim of this study is to summarize... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth defined as delivery before 37 gestational weeks is a leading cause of neonatal and infant morbidity and mortality. The aim of this study is to summarize the evidence from meta-analyses of observational studies on risk factors associated with PTB, evaluate whether there are indications of biases in this literature, and identify which of the previously reported associations are supported by robust evidence.
METHODS
We searched PubMed and Scopus until February 2021, in order to identify meta-analyses examining associations between risk factors and PTB. For each meta-analysis, we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. Evidence was graded as robust, highly suggestive, suggestive, and weak.
RESULTS
Eighty-five eligible meta-analyses were identified, which included 1480 primary studies providing data on 166 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections, and vaccines. Ninety-nine (59.3%) associations were significant at P < 0.05, while 41 (24.7%) were significant at P < 10. Ninety-one (54.8%) associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in 37 (22.3%) and 12 (7.2%) associations, respectively. We evaluated all associations according to prespecified criteria. Seven risk factors provided robust evidence: amphetamine exposure, isolated single umbilical artery, maternal personality disorder, sleep-disordered breathing (SDB), prior induced termination of pregnancy with vacuum aspiration (I-TOP with VA), low gestational weight gain (GWG), and interpregnancy interval (IPI) following miscarriage < 6 months.
CONCLUSIONS
The results from the synthesis of observational studies suggest that seven risk factors for PTB are supported by robust evidence. Routine screening for sleep quality and mental health is currently lacking from prenatal visits and should be introduced. This assessment can promote the development and training of prediction models using robust risk factors that could improve risk stratification and guide cost-effective preventive strategies.
TRIAL REGISTRATION
PROSPERO 2021 CRD42021227296.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Induced; Observational Studies as Topic; Premature Birth; Risk Factors
PubMed: 38093369
DOI: 10.1186/s12916-023-03171-4 -
Revue Medicale de Liege Jun 2024Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health... (Review)
Review
Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health issue. From before conception to long term follow up, many health actors are engaged in this preventive strategy with the same goal : to give the best quality of life for these vulnerable young patients. We will review different preventive aspects during antenatal and perinatal period, during NICU (Neonatal Intensive Care Unit) stay and after discharge. Prevention of prematurity's complications requires a global approach including respiratory, nutritional and infectious aspects among others. Neuroprotective strategies are a key point of this global approach.
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Premature; Pregnancy; Female; Premature Birth
PubMed: 38869136
DOI: No ID Found -
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 -
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 -
Reproductive Sciences (Thousand Oaks,... Dec 2023Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in... (Review)
Review
Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in children under 5 years. PTB is a complex disease with multiple risk factors including genetic variation. Much research has aimed to establish the biological mechanisms underlying PTB often through identification of genetic markers for PTB risk. The objective of this review is to present a comprehensive and updated summary of the published data relating to the field of PTB genetics. A literature search in PubMed was conducted and English studies related to PTB genetics were included. Genetic studies have identified genes within inflammatory, immunological, tissue remodeling, endocrine, metabolic, and vascular pathways that may be involved in PTB. However, a substantial proportion of published data have been largely inconclusive and multiple studies had limited power to detect associations. On the contrary, a few large hypothesis-free approaches have identified and replicated multiple novel variants associated with PTB in different cohorts. Overall, attempts to predict PTB using single "-omics" datasets including genomic, transcriptomic, and epigenomic biomarkers have been mostly unsuccessful and have failed to translate to the clinical setting. Integration of data from multiple "-omics" datasets has yielded the most promising results.
Topics: Female; Child; Humans; Infant, Newborn; Child, Preschool; Premature Birth; Risk Factors; Gene Expression Profiling; Transcriptome; Gestational Age
PubMed: 37450251
DOI: 10.1007/s43032-023-01287-9 -
Journal of Advanced Research Sep 2023Preterm birth is the leading cause of death in children under the age of five. One of the major factors contributing to the high risk of diseases and deaths in premature... (Review)
Review
BACKGROUND
Preterm birth is the leading cause of death in children under the age of five. One of the major factors contributing to the high risk of diseases and deaths in premature infants is the incomplete development of the intestinal immune system. The gut microbiota has been widely recognized as a critical factor in promoting the development and function of the intestinal immune system after birth. However, the gut microbiota of premature infants is at high risk of dysbiosis, which is highly associated with adverse effects on the development and education of the early life immune system. Early intervention can modulate the colonization and development of gut microbiota and has a long-term influence on the development of the intestinal immune system.
AIM OF REVIEW
This review aims to summarize the characterization, interconnection, and underlying mechanism of gut microbiota and intestinal innate immunity in premature infants, and to discuss the status, applicability, safety, and prospects of different intervention strategies in premature infants, thus providing an overview and outlook of the current applications and remaining gaps of early intervention strategies in premature infants.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review is focused on three key concepts. Firstly, the gut microbiota of premature infants is at high risk of dysbiosis, resulting in dysfunctional intestinal immune system processes. Secondly, contributing roles of early intervention have been observed in improving the intestinal environment and promoting gut microbiota colonization, which is significant in the development and function of gut immunity in premature infants. Thirdly, different strategies of early intervention, such as probiotics, fecal microbiota transplantation, and nutrients, show different safety, applicability, and outcome in premature infants, and the underlying mechanism is complex and poorly understood.
Topics: Infant; Female; Child; Infant, Newborn; Humans; Gastrointestinal Microbiome; Dysbiosis; Premature Birth; Infant, Premature; Gastrointestinal Tract
PubMed: 36372205
DOI: 10.1016/j.jare.2022.11.004 -
The Journal of Maternal-fetal &... Dec 2023COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for...
OBJECTIVE
COVID-19 has been reported to increase the risk of prematurity, however, due to the frequent absence of unaffected controls as well as inadequate accounting for confounders in many studies, the question requires further investigation. We sought to determine the impact of COVID-19 disease on preterm birth (PTB) overall, as well as related subcategories such as early prematurity, spontaneous, medically indicated preterm birth, and preterm labor (PTL). We assessed the impact of confounders such as COVID-19 risk factors, a-priori risk factors for PTB, symptomatology, and disease severity on rates of prematurity.
METHODS
This was a retrospective cohort study of pregnant women from March 2020 till October 1st, 2020. The study included patients from 14 obstetric centers in Michigan, USA. Cases were defined as women diagnosed with COVID-19 at any point during their pregnancy. Cases were matched with uninfected women who delivered in the same unit, within 30 d of the delivery of the index case. Outcomes of interest were frequencies of prematurity overall and subcategories of preterm birth (early, spontaneous/medically indicated, preterm labor, and premature preterm rupture of membranes) in cases compared to controls. The impact of modifiers of these outcomes was documented with extensive control for potential confounders. A value <.05 was used to infer significance.
RESULTS
The rate of prematurity was 8.9% in controls, 9.4% in asymptomatic cases, 26.5% in symptomatic COVID-19 cases, and 58.8% among cases admitted to the ICU. Gestational age at delivery was noted to decrease with disease severity. Cases were at an increased risk of prematurity overall [adjusted relative risk (aRR) = 1.62 (1.2-2.18)] and of early prematurity (<34 weeks) [aRR = 1.8 (1.02-3.16)] when compared to controls. Medically indicated prematurity related to preeclampsia [aRR = 2.46 (1.47-4.12)] or other indications [aRR = 2.32 (1.12-4.79)], were the primary drivers of overall prematurity risk. Symptomatic cases were at an increased risk of preterm labor [aRR = 1.74 (1.04-2.8)] and spontaneous preterm birth due to premature preterm rupture of membranes [aRR = 2.2(1.05-4.55)] when compared to controls and asymptomatic cases combined. The gestational age at delivery followed a dose-response relation with disease severity, as more severe cases tended to deliver earlier (Wilcoxon < .05).
CONCLUSIONS
COVID-19 is an independent risk factor for preterm birth. The increased preterm birth rate in COVID-19 was primarily driven by medically indicated delivery, with preeclampsia as the principal risk factor. Symptomatic status and disease severity were significant drivers of preterm birth.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Premature Birth; Retrospective Studies; Michigan; Pre-Eclampsia; COVID-19; SARS-CoV-2; Obstetric Labor, Premature; Pregnancy Outcome
PubMed: 37217448
DOI: 10.1080/14767058.2023.2199343 -
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 -
Nature Communications Nov 2023The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a...
The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth.
Topics: Animals; Female; Humans; Infant, Newborn; Mice; Pregnancy; Biochemical Phenomena; Labor, Obstetric; Parturition; Premature Birth; Uterus
PubMed: 37963860
DOI: 10.1038/s41467-023-43102-8 -
Clinics in Perinatology Jun 2024The complexity of preterm birth (PTB), both spontaneous and medically indicated, and its various etiologies and associated risk factors pose a significant challenge for... (Review)
Review
The complexity of preterm birth (PTB), both spontaneous and medically indicated, and its various etiologies and associated risk factors pose a significant challenge for developing tools to accurately predict risk. This review focuses on the discovery of proteomics signatures that might be useful for predicting spontaneous PTB or preeclampsia, which often results in PTB. We describe methods for proteomics analyses, proteomics biomarker candidates that have so far been identified, obstacles for discovering biomarkers that are sufficiently accurate for clinical use, and the derivation of composite signatures including clinical parameters to increase predictive power.
Topics: Humans; Proteomics; Premature Birth; Female; Pregnancy; Biomarkers; Pre-Eclampsia; Infant, Newborn; Predictive Value of Tests
PubMed: 38705648
DOI: 10.1016/j.clp.2024.02.011