The genetics of preterm birth: using what we know to design better association studies.
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ABSTRACT:
SUBMITTER: Weinberg CR
PROVIDER: S-EPMC2800265 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC10692032 | biostudies-literature
Project description:Preterm birth (PTB) is defined as childbirth occurring at less than 37 completed weeks or 259 days of gestation. Premature babies have higher rates of cerebral palsy, sensory deficits, learning disabilities and respiratory illnesses that extend into adulthood. This lifelong morbidity results in high economic and social costs to families and communities. PTB is a syndrome initiated by multiple mechanisms, including infection or inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress, and other immunologically mediated processes. Identifying and monitoring molecular signals in easily accessible body fluids that can diagnose or predict the risk of preterm labor in pregnant women will reduce or prevent PTBs. A number of studies reported the identification of putative biomarkers for PTB including protein, miRNA and hormone from different body fluids such as serum/plasma, cervical vaginal fluid, saliva and amniotic fluids. These putative biomarkers identified can largely be grouped into three main functional categories: inflammatory related molecules, placenta or fetal derived molecules and stress related molecules. In the past few years next generation sequencing (NGS) has become the major platform for miRNA analysis especially with body fluids. However, studies have shown significant sequence bias among different small RNA library preparation protocols. We have modified the small RNA library construction protocol which greatly reduces the sequence bias and increase miRNA coverage in sample. We also adapted a newly developed size exclusion chromatography (SEC) based EV purification protocol which can provide cleaner EVs compared to other methods. We are using these improved approaches to gain more reliable profile of circulating RNA in body fluid as well as its associated EVs. With these new approaches, we explore the possibility of using specific circulating miRNAs, specifically those encapsulated in EVs, as a noninvasive biomarker for PTB by comparing the miRNA profiles in maternal plasma, EV and EV-depleted plasma between individuals who had a spontaneous preterm birth and uncomplicated pregnancies.
2018-03-19 | GSE106224 | GEO
Project description:A strength of time-series analyses is the inherent control of individual-level risk factors that do not vary temporally. However, in studies of adverse pregnancy outcomes, risk factors considered time-invariant at the individual level may vary seasonally when aggregated into a pregnancy risk set. To illustrate, we describe the seasonal patterns of birth in Atlanta and demonstrate how these patterns could lead to confounding in time-series studies of seasonally-varying exposures and preterm birth.The study cohort included all births in 20-county metropolitan Atlanta delivered during the period 1994-2004 (n = 715,875). We assessed the seasonal patterns of estimated conception and birth for the full cohort and for subgroups stratified by sociodemographic factors. Based on the observed patterns, we quantified the degree of potential confounding created by (1) differences in the gestational age distribution in the risk set across calendar months and (2) differences in the sociodemographic composition of the risk set across calendar months.The overall seasonal pattern of birth was characterized by a peak in August-September and troughs in April-May and November-January. Seasonal patterns differed among racial and ethnic groups, maternal education levels, and marital status. As a consequence of these seasonal patterns, systematic seasonal differences in the gestational age distribution and the sociodemographic composition of the risk set led to differences in expected rates of preterm birth across calendar months.Time-series investigations of seasonally-varying exposures and adverse pregnancy outcomes should consider the potential for bias due to seasonal heterogeneity in the risk set.
| S-EPMC3743217 | biostudies-literature
Project description:Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth on DNA methylation. Genome-wide DNAm was measured using the Illumina 450K array in cord blood samples obtained from 72 full term and 18 preterm newborns. Lymphocyte composition was calculated based on specific epigenetic markers that are present on the 450k array. Differential methylation analysis was performed both at site and region level, moreover Stochastic Epigenetic Mutations (SEMs) were also evaluated. The study showed significant differences in blood cell composition between the two groups. Moreover, after multiple testing correction, statistically significant differences in DNA methylation levels emerged between the two groups both at site and region levels. Results obtained have been compared to those obtained by previous EWAS and a list of genes have been found to be consistent. The SEMs analysis revealed that the burden of SEMs resulted significantly higher in the preterm group. In conclusion, PTB resulted associated to specific epigenetic signatures that involve immune system. Moreover, SEMs analysis revealed an increased epigenetic drift at birth in the preterm group.
2020-07-20 | GSE152380 | GEO
Project description:Transcriptome analysis of preterm and term placentas
2021-08-10 | GSE120480 | GEO
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.
2014-08-28 | PXD001268 | Pride
Project description:Next-generation sequencing is becoming the primary discovery tool in human genetics. There have been many clear successes in identifying genes that are responsible for Mendelian diseases, and sequencing approaches are now poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that predispose individuals to more common complex diseases. There are, however, growing concerns that the complexity and magnitude of complete sequence data could lead to an explosion of weakly justified claims of association between genetic variants and disease. Here, we provide an overview of the basic workflow in next-generation sequencing studies and emphasize, where possible, measures and considerations that facilitate accurate inferences from human sequencing studies.
| S-EPMC4117319 | biostudies-literature
Project description:ImportanceLow birth weight and preterm birth are associated with adverse consequences including increased risk of infant mortality and chronic health conditions. Black infants are more likely than white infants to be born prematurely, which has been associated with disparities in infant mortality and other chronic conditions.ObjectiveTo evaluate whether Medicaid expansion was associated with changes in rates of low birth weight and preterm birth outcomes, both overall and by race/ethnicity.Design, setting, and participantsUsing US population-based data from the National Center for Health Statistics Birth Data Files (2011-2016), difference-in-differences (DID) and difference-in-difference-in-differences (DDD) models were estimated using multivariable linear probability regressions to compare birth outcomes among infants in Medicaid expansion states relative to non-Medicaid expansion states and changes in relative disparities among racial/ethnic minorities for singleton live births to women aged 19 years and older.ExposuresState Medicaid expansion status and racial/ethnic category.Main outcomes and measuresPreterm birth (<37 weeks' gestation), very preterm birth (<32 weeks' gestation), low birth weight (<2500 g), and very low birth weight (<1500 g).ResultsThe final sample of 15 631 174 births (white infants: 8 244 924, black infants: 2 201 658, and Hispanic infants: 3 944 665) came from the District of Columbia and 18 states that expanded Medicaid (n = 8 530 751) and 17 states that did not (n = 7 100 423). In the DID analyses, there were no significant changes in preterm birth in expansion relative to nonexpansion states (preexpansion to postexpansion period, 6.80% to 6.67% [difference: -0.12] vs 7.86% to 7.78% [difference: -0.08]; adjusted DID: 0.00 percentage points [95% CI, -0.14 to 0.15], P = .98), very preterm birth (0.87% to 0.83% [difference: -0.04] vs 1.02% to 1.03% [difference: 0.01]; adjusted DID: -0.02 percentage points [95% CI, -0.05 to 0.02], P = .37), low birth weight (5.41% to 5.36% [difference: -0.05] vs 6.06% to 6.18% [difference: 0.11]; adjusted DID: -0.08 percentage points [95% CI, -0.20 to 0.04], P = .20), or very low birth weight (0.76% to 0.72% [difference: -0.03] vs 0.88% to 0.90% [difference: 0.02]; adjusted DID: -0.03 percentage points [95% CI, -0.06 to 0.01], P = .14). Disparities for black infants relative to white infants in Medicaid expansion states compared with nonexpansion states declined for all 4 outcomes, indicated by a negative DDD coefficient for preterm birth (-0.43 percentage points [95% CI, -0.84 to -0.02], P = .05), very preterm birth (-0.14 percentage points [95% CI, -0.26 to -0.02], P = .03), low birth weight (-0.53 percentage points [95% CI, -0.96 to -0.10], P = .02), and very low birth weight (-0.13 percentage points [95% CI, -0.25 to -0.01], P = .04). There were no changes in relative disparities for Hispanic infants.Conclusions and relevanceBased on data from 2011-2016, state Medicaid expansion was not significantly associated with differences in rates of low birth weight or preterm birth outcomes overall, although there were significant improvements in relative disparities for black infants compared with white infants in states that expanded Medicaid vs those that did not.
| S-EPMC6487545 | biostudies-literature
Project description:There has been an increase in preterm (PT) births in Western countries in recent years, which is associated with low-birthweight (LBW) children. The aim of this study was to determine the association between maternal factors and PT and LBW Chilean newborns. Methods: This was an analytical cross-sectional study of a national sample of 903,847 newborns and their mothers. The newborn gestational age, birth weight, maternal age, marital status, education, employment situation, and residence were analyzed. A multivariate logistic regression model was applied (α = 0.05) (STATA v.15). The prevalence was 6.8% and 5.0% for PT and LBW, respectively. The probability of the newborns being PT and LBW was 1.18 and 1.22 times if their mothers had <12 years of education and 1.38 and 1.29 times if the mothers were ≥35 years old, respectively. Mothers with <12 years education and ≥35 years were risk factors for PT and LBW newborns. Maternal educational attainment was a protective factor for the Chilean newborns, and a maternal age ≥35 years was a risk factor for PT and LBW.
| S-EPMC9319480 | biostudies-literature
Project description:BackgroundThe small sample sizes available within many very preterm (VPT) longitudinal birth cohort studies mean that it is often necessary to combine and harmonise data from individual studies to increase statistical power, especially for studying rare outcomes. Curating and mapping data is a vital first step in the process of data harmonisation. To facilitate data mapping and harmonisation across VPT birth cohort studies, we developed a custom classification system as part of the Research on European Children and Adults born Preterm (RECAP Preterm) project in order to increase the scope and generalisability of research and the evaluation of outcomes across the lifespan for individuals born VPT.MethodsThe multidisciplinary consortium of expert clinicians and researchers who made up the RECAP Preterm project participated in a four-phase consultation process via email questionnaire to develop a topic-specific classification system. Descriptive analyses were calculated after each questionnaire round to provide pre- and post- ratings to assess levels of agreement with the classification system as it developed. Amendments and refinements were made to the classification system after each round.ResultsExpert input from 23 clinicians and researchers from the RECAP Preterm project aided development of the classification system's topic content, refining it from 10 modules, 48 themes and 197 domains to 14 modules, 93 themes and 345 domains. Supplementary classifications for target, source, mode and instrument were also developed to capture additional variable-level information. Over 22,000 individual data variables relating to VPT birth outcomes have been mapped to the classification system to date to facilitate data harmonisation. This will continue to increase as retrospective data items are mapped and harmonised variables are created.ConclusionsThis bespoke preterm birth classification system is a fundamental component of the RECAP Preterm project's web-based interactive platform. It is freely available for use worldwide by those interested in research into the long term impact of VPT birth. It can also be used to inform the development of future cohort studies.
| S-EPMC8742427 | biostudies-literature