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PLoS Medicine Aug 2023The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin... (Meta-Analysis)
Meta-Analysis
Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.
BACKGROUND
The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies.
METHODS AND FINDINGS
Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low.
CONCLUSIONS
Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cerclage, Cervical; Cervix Uteri; Labor Stage, First; Pregnancy, Twin; Premature Birth
PubMed: 37535682
DOI: 10.1371/journal.pmed.1004266 -
Epigenetics Dec 2023'Epigenetic clocks' have been developed to accurately predict chronologic gestational age and have been associated with child health outcomes in prior work. We... (Meta-Analysis)
Meta-Analysis
'Epigenetic clocks' have been developed to accurately predict chronologic gestational age and have been associated with child health outcomes in prior work. We meta-analysed results from four prospective U.S cohorts investigating the association between epigenetic age acceleration estimated using blood DNA methylation collected at birth and preschool age Childhood Behavior Checklist (CBCL) scores. Epigenetic ageing was not significantly associated with CBCL total problem scores (β = 0.33, 95% CI: -0.95, 0.28) and DSM-oriented pervasive development problem scores (β = -0.23, 95% CI: -0.61, 0.15). No associations were observed for other DSM-oriented subscales. The meta-analysis results suggest that epigenetic gestational age acceleration is not associated with child emotional and behavioural functioning for preschool age group. These findings may relate to our study population, which includes two cohorts enriched for ASD and one preterm birth cohort.; future work should address the role of epigenetic age in child health in other study populations. DNAm: DNA methylation; CBCL: Child Behavioral Checklist; ECHO: Environmental Influences on Child Health Outcomes; EARLI: Early Autism Risk Longitudinal Investigation; MARBLES: Markers of Autism Risk in Babies - Learning Early Signs; ELGAN: Extremely Low Gestational Age Newborns; ASD: autism spectrum disorder; BMI: body mass index; DSM: Diagnostic and Statistical Manual of Mental Disorders.
Topics: Child, Preschool; Humans; Infant, Newborn; Autism Spectrum Disorder; DNA Methylation; Epigenesis, Genetic; Premature Birth; Prospective Studies
PubMed: 37691382
DOI: 10.1080/15592294.2023.2254971 -
Taiwanese Journal of Obstetrics &... Sep 2023To evaluate the safety and efficacy of atosiban and ritodrine in pregnant women who were hospitalized for threatened preterm labor (TPL).
A multicenter, retrospective comparison of pregnancy outcomes between groups of preterm labor nulliparous mothers treated with atosiban vs. ritodrine in singleton and multiple pregnancies.
OBJECTIVE
To evaluate the safety and efficacy of atosiban and ritodrine in pregnant women who were hospitalized for threatened preterm labor (TPL).
MATERIALS AND METHODS
Diagnosis records of preterm labor and subsequent pregnancy-related records and medical records of newborns were extracted from the Clinical Data Warehouse of the Catholic Medical Center's affiliated hospital. Since 2009, cases of preterm labor diagnosed before 34 weeks of pregnancy for first-time mothers who delivered at any one of three hospitals and who received drug treatment for more than 2 days to delay delivery were included in the dataset. Based on characteristics of Korea's national health insurance system, the drug treatment after diagnosis of preterm labor could be classified into cases using only ritodrine (571 women), cases using only atosiban (244 women), and cases where ritodrine treatment was started and then changed to atosiban (275 women). Demographic factors, obstetric outcomes, neonatal outcomes of the two groups were analyzed.
RESULTS
The duration and maintenance of pregnancy were found to be similar between the two groups, although the initial cervical length was significantly shorter in the atosiban cohort (AC). Only in multifetal pregnancies, the maintenance of pregnancy was significantly longer in the AC. The total duration of pregnancy did not show any significant difference between the two groups regardless of singleton or multiple pregnancy. However, the distribution graph showed non-responders in the ritodrine cohort (RC). Our study showed a difference in neonatal birth weight of singleton between the two groups. The length of hospitalization and the NICU admission rate were also significantly higher in the RC for singleton. Although not significant, the proportion of numbers with an Apgar score less than 7 was higher in the RC. Neonatal death was more common in the RG (8 cases in AC and 18 cases in RC).
CONCLUSIONS
Using atosiban for TPL is more effective than using ritodrine for maintaining pregnancy in the case of a multifetal pregnancy. In singleton pregnancies, neonatal outcomes of the atosiban group were superior to those of the ritodrine group. There seems to be a non-responder group when using ritodrine for TPL. Further studies are needed to determine causes of non-responders of ritodrine and effects of ritodrine on the fetus.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Ritodrine; Mothers; Pregnancy Outcome; Retrospective Studies; Pregnancy, Multiple; Obstetric Labor, Premature
PubMed: 37678995
DOI: 10.1016/j.tjog.2023.07.009 -
Korean Journal of Women Health Nursing Sep 2023Preterm birth is increasing, and obstetric nurses should have the competency to provide timely care. Therefore, training is necessary in the maternal nursing practicum....
Does a preterm labor-assessment algorithm improve preterm labor-related knowledge, clinical practice confidence, and educational satisfaction?: a quasi-experimental study.
PURPOSE
Preterm birth is increasing, and obstetric nurses should have the competency to provide timely care. Therefore, training is necessary in the maternal nursing practicum. This study aimed to investigate the effects of practice education using a preterm-labor assessment algorithm on preterm labor-related knowledge and clinical practice confidence in senior nursing students.
METHODS
A pre-post quasi-experimental design with three groups was used for 61 students. The preterm-labor assessment algorithm was modified into three modules from the preterm-labor assessment algorithm by March of Dimes. We evaluated preterm labor-related knowledge, clinical practice confidence, and educational satisfaction. Data were analyzed with the paired t-test and repeated-measures analysis of variance.
RESULTS
The practice education using a preterm-labor assessment algorithm significantly improved both preterm labor-related knowledge and clinical practice confidence (paired t=-7.17, p<.001; paired t=-5.51, p<.001, respectively). The effects of the practice education using a preterm-labor assessment algorithm on knowledge lasted until 8 weeks but decreased significantly at 11 and 13 weeks after the program, while the clinical practice confidence significantly decreased at 8 weeks post-program.
CONCLUSION
The practice education using a preterm-labor assessment algorithm was effective in improving preterm labor-related knowledge and clinical practice confidence. The findings suggest that follow-up education should be conducted at 8 weeks, or as soon as possible thereafter, to maintain knowledge and clinical confidence, and the effects should be evaluated.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Premature Birth; Obstetric Labor, Premature; Mental Processes; Personal Satisfaction; Algorithms
PubMed: 37813665
DOI: 10.4069/kjwhn.2023.08.17 -
Reproductive Sciences (Thousand Oaks,... Mar 2024Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile... (Review)
Review
Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile properties necessary for the normal functioning of the uterus. Cross-linking is a fundamental step in collagen biosynthesis and is critical for its normal biophysical properties. This step occurs enzymatically via lysyl oxidase (LOX) or non-enzymatically with the production of advanced glycation end-products (AGEs). Cross-links found in uterine tissue include the reducible dehydro-dihydroxylysinonorleucine (deH-DHLNL), dehydro-hydroxylysinonorleucine (deH-HLNL), and histidinohydroxymerodesmosine (HHMD); and the non-reducible pyridinoline (PYD), deoxy-pyridinoline (DPD); and a trace of pentosidine (PEN). Collagen cross-links are instrumental for uterine tissue integrity and the continuation of a healthy pregnancy. Decreased cervical cross-link density is observed in preterm birth, whereas increased tissue stiffness caused by increased cross-link density is a pathogenic feature of uterine fibroids. AGEs disrupt embryo development, decidualization, implantation, and trophoblast invasion. Uterine collagen cross-linking regulators include steroid hormones, such as progesterone and estrogen, prostaglandins, proteoglycans, metalloproteinases, lysyl oxidases, nitric oxide, nicotine, and vitamin D. Thus, uterine collagen cross-linking presents an opportunity to design therapeutic targets and warrants further investigation in common uterine disorders, such as uterine fibroids, cervical insufficiency, preterm birth, dystocia, endometriosis, and adenomyosis.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Premature Birth; Collagen; Cervix Uteri; Leiomyoma; Biology
PubMed: 37907804
DOI: 10.1007/s43032-023-01386-7 -
The Lancet. Planetary Health Feb 2024Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological...
BACKGROUND
Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs.
METHODS
In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery.
FINDINGS
We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion).
INTERPRETATION
In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class.
FUNDING
National Institutes of Health.
Topics: United States; Pregnancy; Female; Humans; Infant, Newborn; Premature Birth; Birth Weight; Diethylhexyl Phthalate; Pregnancy Complications; Phthalic Acids
PubMed: 38331533
DOI: 10.1016/S2542-5196(23)00270-X -
The New England Journal of Medicine Nov 2023
Topics: Female; Infant, Newborn; Humans; Premature Birth; Gestational Age; Neurologic Examination
PubMed: 37937792
DOI: 10.1056/NEJMc2310222 -
Schizophrenia Research Dec 2023Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have attempted to find an association between schizophrenia and obstetric complications, with varying results.
OBJECTIVE
The primary objective of this systematic review and meta-analyses was to summarize the relationship between maternal schizophrenia and perinatal pregnancy outcomes.
DATA SOURCES
PubMed, Web of Science and Ovid EMBASE were searched from January 2001 to September 2022 using keywords related to pregnancy, women, schizophrenia.
STUDY SELECTION
A total of 23 independent studies across 21,253 individuals with schizophrenia were identified and included in the analysis.
DATA EXTRACTION
The following data were extracted: author, year of publication, country/continent of data collection, study design, demographic characteristics, diagnoses criteria, related complications. Data were analyzed using random-effects pairwise meta-analysis and were reported as prevalence and odd ratios (OR). Statistical heterogeneity was quantified with the I statistic.
RESULTS
The prevalence of adverse perinatal pregnancy outcomes was represented in descending order: cesarean section (26.0 %); labor induction (24.0 %); small for gestational age (10.5 %); gestational diabetes mellitus (9.2 %); preterm birth (9.1 %); low birth weight (7.8 %); preterm rupture of membranes (6.1 %); 1-Minute Apgar Score < 7 (5.6 %); large for gestational age (5.5 %); birth defect (5.4 %); antepartum hemorrhage (4.4 %);preeclampsia/eclampsia (4.8 %); postpartum hemorrhage (3.9 %); 5-Minute Apgar Score < 7 (3.6 %); gestational hypertension (3.3 %); placental abruption (1.0 %); placenta previa (0.6 %); thromboembolic disease (0.4 %); neonatal mortality (0.3 %) (P ≤ 0.05). There was a higher risk of adverse outcomes including gestational diabetes mellitus, preeclampsia/eclampsia, placental abruption, thromboembolic disease, preterm birth, birth defect, 1-Minute Apgar score < 7, small for gestational age, low birth weight and neonatal mortality compared with non-schizophrenia population (P ≤ 0.05).
CONCLUSIONS
Women with schizophrenia are at higher risk of adverse perinatal pregnancy outcomes. It is imperative that research efforts continue to focus on the reproductive safety of women with schizophrenia during their childbearing years.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pregnancy Outcome; Premature Birth; Diabetes, Gestational; Abruptio Placentae; Cesarean Section; Pre-Eclampsia; Eclampsia; Schizophrenia; Placenta
PubMed: 37979419
DOI: 10.1016/j.schres.2023.11.001 -
Journal of Perinatal Medicine Oct 2023To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery. (Review)
Review
OBJECTIVES
To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery.
METHODS
We conducted a retrospective cohort study to understand what factors predict the optimal timing of ACS administration (ACS administration within seven days). We reviewed consecutive charts of adult pregnant women receiving ACS from January 1, 2011, to December 31, 2019. We excluded pregnancies under 23 weeks, incomplete and duplicate records, and patients delivered outside our health system. The timing of ACS administration was categorized as optimal or suboptimal. These groups were analyzed regarding demographics, indications for ACS administration, risk factors for preterm delivery, and signs and symptoms of preterm labor.
RESULTS
We identified 25,776 deliveries. ACS were administered to 531 pregnancies, of which 478 met the inclusion criteria. Of the 478 pregnancies included in the study, 266 (55.6 %) were delivered in the optimal timeframe. There was a higher proportion of patients receiving ACS for the indication of threatened preterm labor in the suboptimal group as compared to the optimal group (85.4 % vs. 63.5 %, p<0.001). In addition, patients who delivered in the suboptimal timeframe had a higher proportion of short cervix (33 % vs. 6.4 %, p<0.001) and positive fetal fibronectin (19.8 % vs. 1.1 %, p<0.001) compared to those who delivered in the optimal timeframe.
CONCLUSIONS
More emphasis should be placed on the judicious use of ACS. Emphasis should be placed on clinical assessment rather than relying solely on imaging and laboratory tests. Re-appraisal of institutional practices and thoughtful ACS administration based on the risk-benefit ratio is warranted.
Topics: Adult; Infant, Newborn; Female; Humans; Pregnancy; Premature Birth; Retrospective Studies; Prenatal Care; Adrenal Cortex Hormones; Obstetric Labor, Premature
PubMed: 37216498
DOI: 10.1515/jpm-2023-0074 -
BMC Pregnancy and Childbirth Jul 2023There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product...
BACKGROUND
There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.
METHODS
Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.
RESULTS
The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.
CONCLUSIONS
This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.
Topics: Infant, Newborn; Female; Humans; Premature Birth; Progesterone; Obstetric Labor, Premature; Fatty Acids, Omega-3
PubMed: 37464260
DOI: 10.1186/s12884-023-05842-9