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Lancet (London, England) Jan 2008This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born... (Review)
Review
This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
Topics: Body Mass Index; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Premature Birth; Racial Groups; Risk Factors
PubMed: 18177778
DOI: 10.1016/S0140-6736(08)60074-4 -
Clinics in Perinatology Sep 2018With advanced perinatal care and technology, survival among infants born very preterm (<32 weeks gestation) has improved dramatically over the last several decades.... (Review)
Review
With advanced perinatal care and technology, survival among infants born very preterm (<32 weeks gestation) has improved dramatically over the last several decades. However, adverse medical and neurodevelopmental outcomes for those born very preterm remains high, particularly at the lowest gestational ages. Public health plays a critical role in providing data to assess population-based risks associated with very preterm birth, addressing disparities, and identifying opportunities for prevention, including improving the health of reproductive-age women, before, during, and after pregnancy.
Topics: Female; Health Care Costs; Health Status Disparities; Healthcare Disparities; Humans; Infant, Extremely Premature; Infant, Newborn; Neurodevelopmental Disorders; Pregnancy; Premature Birth; Public Health; Quality of Health Care; Risk Factors; Social Determinants of Health
PubMed: 30144856
DOI: 10.1016/j.clp.2018.05.007 -
Reproduction (Cambridge, England) Jun 2022The syndrome of preterm labor comprises multiple established and novel etiologies. This review summarizes the distinct immune mechanisms implicated in preterm labor and... (Review)
Review
IN BRIEF
The syndrome of preterm labor comprises multiple established and novel etiologies. This review summarizes the distinct immune mechanisms implicated in preterm labor and birth and highlights potential strategies for its prevention.
ABSTRACT
Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, results from preterm labor, a syndrome that includes multiple etiologies. In this review, we have summarized the immune mechanisms implicated in intra-amniotic inflammation, the best-characterized cause of preterm labor and birth, as well as novel etiologies non-associated with intra-amniotic inflammation (i.e. formally known as idiopathic). While the intra-amniotic inflammatory responses driven by microbes (infection) or alarmins (sterile) have some overlap in the participating cellular and molecular processes, the distinct natures of these two conditions necessitate the implementation of specific approaches to prevent adverse pregnancy and neonatal outcomes. Intra-amniotic infection can be treated with the correct antibiotics, whereas sterile intra-amniotic inflammation could potentially be treated by administering a combination of anti-inflammatory drugs (e.g. betamethasone, inflammasome inhibitors, etc.). Recent evidence also supports the role of fetal T-cell activation as a newly described trigger for preterm labor and birth in a subset of cases diagnosed as idiopathic. Moreover, herein we also provide evidence of two maternally-driven immune mechanisms responsible for preterm births formerly considered to be idiopathic. First, the impairment of maternal Tregs can lead to preterm birth, likely due to the loss of immunosuppressive activity resulting in unleashed effector T-cell responses. Secondly, homeostatic macrophages were shown to be essential for maintaining pregnancy and promoting fetal development, and the adoptive transfer of homeostatic M2-polarized macrophages shows great promise for preventing inflammation-induced preterm birth. Collectively, in this review, we discuss the established and novel immune mechanisms responsible for preterm birth and highlight the potential targets for novel strategies aimed at preventing the multi-etiological syndrome of preterm labor leading to preterm birth.
Topics: Female; Homeostasis; Humans; Infant, Newborn; Inflammation; Obstetric Labor, Premature; Parturition; Pregnancy; Premature Birth
PubMed: 35559791
DOI: 10.1530/REP-22-0046 -
American Journal of Obstetrics and... Sep 2022To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of... (Meta-Analysis)
Meta-Analysis Review
Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis.
OBJECTIVE
To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
DATA SOURCES
MEDLINE, Embase, LILACS, and CINAHL (from their inception to February 28, 2022), Cochrane databases, Google Scholar, bibliographies, and conference proceedings.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth.
METHODS
The primary outcomes were preterm birth <37 and <34 weeks of gestation. The secondary outcomes included adverse maternal and perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in the included studies, heterogeneity (I test), small-study effects, publication bias, and quality of evidence; performed subgroup and sensitivity analyses; and calculated 95% prediction intervals and adjusted relative risks.
RESULTS
Ten studies (2958 women) met the inclusion criteria: 7 with a sample size <150 (small studies) and 3 with a sample size >600 (large studies). Among the 7 small studies, 4 were at high risk of bias, 2 were at some concerns of bias, and only 1 was at low risk of bias. All the large studies were at low risk of bias. Vaginal progesterone significantly decreased the risk of preterm birth <37 weeks (relative risk, 0.64; 95% confidence interval, 0.50-0.81; I=75%; 95% prediction interval, 0.31-1.32; very low-quality evidence) and <34 weeks (relative risk, 0.62; 95% confidence interval, 0.42-0.92; I=66%; 95% prediction interval, 0.23-1.68; very low-quality evidence), and the risk of admission to the neonatal intensive care unit (relative risk, 0.53; 95% confidence interval, 0.33-0.85; I=67%; 95% prediction interval, 0.16-1.79; low-quality evidence). There were no significant differences between the vaginal progesterone and the placebo or no treatment groups in other adverse perinatal and maternal outcomes. Subgroup analyses revealed that vaginal progesterone decreased the risk of preterm birth <37 weeks (relative risk, 0.43; 95% confidence interval, 0.33-0.55; I=0%) and <34 weeks (relative risk, 0.27; 95% confidence interval, 0.15-0.49; I=0%) in the small but not in the large studies (relative risk, 0.98; 95% confidence interval, 0.88-1.09; I=0% for preterm birth <37 weeks; and relative risk, 0.94; 95% confidence interval, 0.78-1.13; I=0% for preterm birth <34 weeks). Sensitivity analyses restricted to studies at low risk of bias indicated that vaginal progesterone did not reduce the risk of preterm birth <37 weeks (relative risk, 0.96; 95% confidence interval, 0.84-1.09) and <34 weeks (relative risk, 0.90; 95% confidence interval, 0.71-1.15). There was clear evidence of substantial small-study effects in the meta-analyses of preterm birth <37 and <34 weeks of gestation because of funnel plot asymmetry and the marked differences in the pooled relative risks obtained from fixed-effect and random-effects models. The adjustment for small-study effects resulted in a markedly reduced and nonsignificant effect of vaginal progesterone on preterm birth <37 weeks (relative risk, 0.86; 95% confidence interval, 0.68-1.10) and <34 weeks (relative risk, 0.92; 95% confidence interval, 0.60-1.42).
CONCLUSION
There is no convincing evidence supporting the use of vaginal progesterone to prevent recurrent preterm birth or to improve perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
Topics: Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Pregnancy; Premature Birth; Progesterone; Vagina
PubMed: 35460628
DOI: 10.1016/j.ajog.2022.04.023 -
Obstetrics and Gynecology Dec 2021
Topics: Humans; Infant, Newborn; Obstetric Labor, Premature; Premature Birth
PubMed: 34794160
DOI: 10.1097/AOG.0000000000004612 -
Advanced Drug Delivery Reviews Jul 2021Preterm birth (PTB) is defined as delivery before 37 weeks of gestation. Globally, 15 million infants are born prematurely, putting these children at an increased risk... (Review)
Review
Preterm birth (PTB) is defined as delivery before 37 weeks of gestation. Globally, 15 million infants are born prematurely, putting these children at an increased risk of mortality and lifelong health challenges. Currently in the U.S., there is only one FDA approved therapy for the prevention of preterm birth. Makena is an intramuscular progestin injection given to women who have experienced a premature delivery in the past. Recently, however, Makena failed a confirmatory trial, resulting the Center for Drug Evaluation and Research's (CDER) recommendation for the FDA to withdrawal Makena's approval. This recommendation would leave clinicians with no therapeutic options for preventing PTB. Here, we outline recent interdisciplinary efforts involving physicians, pharmacologists, biologists, chemists, and engineers to understand risk factors associated with PTB, to define mechanisms that contribute to PTB, and to develop next generation therapies for preventing PTB. These advances have the potential to better identify women at risk for PTB, prevent the onset of premature labor, and, ultimately, save infant lives.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Animals; Drug Approval; Drug Development; Female; Humans; Infant, Newborn; Pregnancy; Premature Birth; Progestins; Risk Factors
PubMed: 33895215
DOI: 10.1016/j.addr.2021.04.021 -
Fertility and Sterility Sep 2023Worldwide, more than 10 million children have been born after assisted reproduction technology (ART), comprising up to 7.9% of children born in Europe and up to 5.1 % of... (Review)
Review
Worldwide, more than 10 million children have been born after assisted reproduction technology (ART), comprising up to 7.9% of children born in Europe and up to 5.1 % of children born in the US in 2018. The short-term outcome for children born after ART is well-known from numerous publications, with higher rates of preterm birth and low birth weight in children born after fresh embryo transfer and higher rates of large for gestational age and high birth weight in children born after frozen embryo transfer compared with children born after spontaneous conception. Higher rates of birth defects in children born after ART have also been shown consistently over time. Studies on long-term health outcomes after ART are scarcer but suggest an increased risk of altered blood pressure and cardiovascular function in children born after ART. In this review, we summarize long-term health outcomes in children born after ART and discuss whether the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or ART treatments per se. Finally, we speculate where the future will bring us regarding ART treatment strategies and the safety of the mother and child.
Topics: Pregnancy; Female; Infant, Newborn; Child; Humans; Premature Birth; Pregnancy Outcome; Infant, Premature; Pregnancy, Multiple; Population Surveillance; Reproductive Techniques, Assisted; Mothers
PubMed: 37086833
DOI: 10.1016/j.fertnstert.2023.04.022 -
Cells Aug 2020With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden... (Review)
Review
With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks' gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability). These perinatal insults cause a self-perpetuating cascade of peripheral and cerebral inflammation that plays a critical role in the etiology of diffuse white and grey matter injuries that underlies a spectrum of connectivity deficits in survivors from extremely preterm birth. This review focuses on chorioamnionitis and hypoxia-ischemia, which are two important antenatal risk factors for preterm brain injury, and highlights the latest insights on its pathophysiology, potential treatment, and future perspectives to narrow the translational gap between preclinical research and clinical applications.
Topics: Brain Injuries; Cell- and Tissue-Based Therapy; Chorioamnionitis; Female; Gestational Age; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Incidence; Infant, Newborn; Infant, Premature; Pregnancy; Premature Birth; Time Factors
PubMed: 32785181
DOI: 10.3390/cells9081871 -
American Journal of Obstetrics &... Jan 2023This expert review aimed to assess current literature on the effect and tracking of physical activity during pregnancy and associated outcomes. Self-reported physical... (Review)
Review
This expert review aimed to assess current literature on the effect and tracking of physical activity during pregnancy and associated outcomes. Self-reported physical activity may be inaccurate given the subjective nature of the questionnaires. The accelerometer ActiGraph is considered the "gold standard" to objectively measure physical activity. However, other more user-friendly wearable devices are now widely available and may accurately track physical activity. Conclusive data from both validated activity questionnaires and accelerometers indicate that physical activity is safe during pregnancy. In addition, studies of physical activity during pregnancy that evaluate pregnancy outcomes have found reduced risks of preterm birth, preeclampsia, and gestational diabetes mellitus and improved mental health among individuals who regularly engage in physical activity. In the United States, approximately 48% of pregnant individuals gain more than the recommended amount of weight during pregnancy; excessive gestational weight gain is associated with an increased risk of maternal and fetal complications, including preterm birth, preeclampsia, and gestational diabetes mellitus, and corresponding higher adverse short- and long-term maternal and offspring health outcomes. Although physical activity is safe during pregnancy and may reduce excessive gestational weight gain and resultant pregnancy complications, further research is needed to determine the frequency and duration of specific types of physical activity during pregnancy. Providers should encourage physical activity before and during pregnancy and educate patients regarding the benefits and safety of physical activity.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Diabetes, Gestational; Gestational Weight Gain; Premature Birth; Pre-Eclampsia; Exercise; Weight Gain
PubMed: 36174931
DOI: 10.1016/j.ajogmf.2022.100758 -
Nature Microbiology Feb 2023Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited....
Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Xenobiotics; Vagina; Infant, Premature; Metabolome
PubMed: 36635575
DOI: 10.1038/s41564-022-01293-8