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1.
Am Fam Physician ; 106(3): 337-339, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36125997
2.
Front Endocrinol (Lausanne) ; 13: 921220, 2022.
Article in English | MEDLINE | ID: mdl-36120450

ABSTRACT

Objective: To investigate the risk of preterm birth in women with a placenta previa or a low-lying placenta for different cut-offs of gestational age and to evaluate preventive interventions. Search and methods: MEDLINE, EMBASE, CENTRAL, Web of Science, WHO-ICTRP and clinicaltrials.gov were searched until December 2021. Randomized controlled trials, cohort studies and case-control studies assessing preterm birth in women with placenta previa or low-lying placenta with a placental edge within 2 cm of the internal os in the second or third trimester were eligible for inclusion. Pooled proportions and odds ratios for the risk of preterm birth before 37, 34, 32 and 28 weeks of gestation were calculated. Additionally, the results of the evaluation of preventive interventions for preterm birth in these women are described. Results: In total, 34 studies were included, 24 reporting on preterm birth and 9 on preventive interventions. The pooled proportions were 46% (95% CI [39 - 53%]), 17% (95% CI [11 - 25%]), 10% (95% CI [7 - 13%]) and 2% (95% CI [1 - 3%]), regarding preterm birth <37, <34, <32 and <28 weeks in women with placenta previa. For low-lying placentas the risk of preterm birth was 30% (95% CI [19 - 43%]) and 1% (95% CI [0 - 6%]) before 37 and 34 weeks, respectively. Women with a placenta previa were more likely to have a preterm birth compared to women with a low-lying placenta or women without a placenta previa for all gestational ages. The studies about preventive interventions all showed potential prolongation of pregnancy with the use of intramuscular progesterone, intramuscular progesterone + cerclage or pessary. Conclusions: Both women with a placenta previa and a low-lying placenta have an increased risk of preterm birth. This increased risk is consistent across all severities of preterm birth between 28-37 weeks of gestation. Women with placenta previa have a higher risk of preterm birth than women with a low-lying placenta have. Cervical cerclage, pessary and intramuscular progesterone all might have benefit for both women with placenta previa and low-lying placenta, but data in this population are lacking and inconsistent, so that solid conclusions about their effectiveness cannot be drawn. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42019123675.


Subject(s)
Placenta Previa , Premature Birth , Cervix Uteri , Female , Humans , Infant, Newborn , Placenta , Placenta Previa/epidemiology , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Progesterone
3.
Lancet Glob Health ; 10(10): e1523-e1533, 2022 10.
Article in English | MEDLINE | ID: mdl-36113535

ABSTRACT

BACKGROUND: After considerable debate, there is now unequivocal evidence that use of antenatal corticosteroids improves outcomes in preterm neonates when used in women at risk of early preterm birth in reasonably equipped hospitals in low-resource countries. We aimed to evaluate the cost-effectiveness of dexamethasone administration in the management of preterm birth in a cohort of pregnant women from five low-resource countries. METHODS: We performed a cost-effectiveness analysis using data from 2828 women (and 3051 babies) who participated in the WHO ACTION-I trial, a multicentre, randomised, placebo-controlled trial that assessed the safety and efficacy of dexamethasone in pregnant women at risk of early preterm birth in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. We used a decision tree model to assess the cost-effectiveness of dexamethasone treatment compared with no intervention from a health-care sector perspective. Outcome data were taken from the primary results of the trial and primary data on cost were collected in 28 hospitals. The primary cost-effectiveness outcome was cost per neonatal death or the cost per disability-adjusted life-years (DALYs) averted, or costs saved per 1000 woman-baby units if the intervention was found to be cost-saving. FINDINGS: Administration of dexamethasone averted 38 neonatal deaths per 1000 woman-baby units and 1132 DALYs per 1000 woman-baby units. Compared with no intervention, use of antenatal corticosteroids was cost-saving in all five countries, ranging from a saving of US$1778 per 1000 woman-baby units (95% uncertainty interval [UI] -13 878 to 9483) in Nigeria, to $20 531 per 1000 woman-baby units (-46 387 to 4897) in Pakistan, to $36 870 per 1000 woman-baby units (-61 569 to -15 672) in Bangladesh, to $38 303 per 1000 woman-baby units (-64 183 to -10 753) in India, and to $53 681 per 1000 woman-baby units (-113 822 to 2394) in Kenya. Findings remained consistent following sensitivity analyses. In all five countries, dexamethasone was more effective and cost less compared with no treatment. INTERPRETATION: Antenatal dexamethasone for early preterm birth was cost-saving when used in hospitals in low-resource countries. Decision makers in low-resource settings can be confident that use of antenatal dexamethasone for early preterm birth is cost-effective, and often cost-saving when used in reasonably equipped hospitals in low-resource countries. FUNDING: Bill & Melinda Gates Foundation and WHO.


Subject(s)
Perinatal Death , Premature Birth , Adrenal Cortex Hormones , Cost-Benefit Analysis , Dexamethasone/therapeutic use , Female , Humans , Infant , Infant, Newborn , Pregnancy , Premature Birth/prevention & control , Prenatal Care/methods , World Health Organization
4.
J Clin Pharmacol ; 62 Suppl 1: S79-S93, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36106783

ABSTRACT

Preterm birth (PTB; defined as delivery before 37 weeks of pregnancy) is the leading cause of morbidity and mortality in infants and children aged <5 years, conferring potentially devastating short- and long-term complications. Despite extensive research in the field, there is currently a paucity of medications available for PTB prevention and treatment. Over the past few decades, inflammation in gestational tissues has emerged at the forefront of PTB pathophysiology. Even in the absence of infection, inflammation alone can prematurely activate the main components of parturition resulting in uterine contractions, cervical ripening and dilatation, membrane rupture, and subsequent PTB. Mechanistic studies have identified critical elements of the complex inflammatory molecular pathways involved in PTB. Here, we discuss therapeutic options that target such key mediators with an aim to prevent, postpone, or treat PTB. We provide an overview of more traditional therapies that are currently used or being tested in humans, and we highlight recent advances in preclinical studies introducing novel approaches with therapeutic potential. We conclude that urgent collaborative action is required to address the unmet need of developing effective strategies to tackle the challenge of PTB and its complications.


Subject(s)
Premature Birth , Child , Female , Humans , Infant, Newborn , Inflammation/drug therapy , Pregnancy , Premature Birth/metabolism , Premature Birth/prevention & control
5.
Sci Rep ; 12(1): 15345, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36097276

ABSTRACT

We aimed to evaluate the changes in maternal and neonatal complications such as threatened preterm labor (TPL) and preterm birth before and during the coronavirus disease 2019 (COVID-19) pandemic using large-scale real-world data in Japan. We obtained data from the Japan Medical Data Center claims database and evaluated differences in maternal and neonatal complications, such as the prevalence of TPL and preterm birth before the COVID-19 pandemic (in the year 2018 or 2019) and during the COVID-19 pandemic (in 2020). We included 5533, 6257, and 5956 deliveries in the years 2018, 2019, and 2020, respectively. TPL prevalence and preterm birth had significantly decreased in 2020 (41.3%, 2.6%, respectively) compared with those reported in 2018 (45.3%, 3.9%, respectively) and 2019 (44.5%, 3.8%, respectively). Neonatal outcomes such as low-birth-weight infants and retinopathy of prematurity were also improved during the pandemic. There were no clear trends in the prevalence of maternal complications such as hypertensive disorders of pregnancy; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; and preeclampsia. Oral ritodrine hydrochloride usage in all participants had significantly decreased during the COVID-19 pandemic. In conclusion, our results suggest that the COVID-19 pandemic has ameliorated TPL and consequently reduced the number of preterm births.


Subject(s)
COVID-19 , Obstetric Labor, Premature , Premature Birth , COVID-19/epidemiology , Female , Humans , Infant , Infant, Newborn , Japan/epidemiology , Obstetric Labor, Premature/epidemiology , Pandemics/prevention & control , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Prevalence
6.
Nat Commun ; 13(1): 5190, 2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36057724

ABSTRACT

Preliminary evidence from China and other countries has suggested that coronavirus disease 2019 (COVID-19) mitigation measures have caused a decline in preterm births, but evidence is conflicting. Utilising a national representative data of 11,714,947 pregnant women in China, we explored the immediate changes in preterm birth rates during the COVID-19 mitigation period using an interrupted-time-series analysis. We defined the period prior to February 1, 2020 as the baseline, followed by the COVID-19 mitigation stage. In the first month of the COVID-19 mitigation, a significant absolute decrease in preterm birth rates of 0.68% (95%CI:-1.10% to -0.26%) in singleton, and of 2.80% (95%CI:-4.51% to -1.09%) in multiple births was noted. This immediate decline in Wuhan was greater than that at the national level among singleton births [-2.21% (95%CI:-4.09% to -0.34% vs. -0.68%)]. Here we report an immediate impact of COVID-19 mitigation measures on preterm birth in China.


Subject(s)
COVID-19 , Premature Birth , COVID-19/epidemiology , COVID-19/prevention & control , Female , Humans , Infant, Newborn , Interrupted Time Series Analysis , Pregnancy , Pregnancy, Multiple , Pregnant Women , Premature Birth/epidemiology , Premature Birth/prevention & control
7.
BMC Pregnancy Childbirth ; 22(1): 669, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36042432

ABSTRACT

OBJECTIVES: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. METHODS: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. RESULTS: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. CONCLUSIONS: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.


Subject(s)
Pregnancy, Triplet , Premature Birth , Cervical Length Measurement , Cervix Uteri/diagnostic imaging , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Premature Birth/diagnosis , Premature Birth/epidemiology , Premature Birth/prevention & control , Reference Values , Retrospective Studies
8.
J Perinat Med ; 50(7): 970-976, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36027908

ABSTRACT

OBJECTIVES: The US preterm birth rate varies dramatically by race and ethnicity yet the racial and ethnic representation within studies evaluating 17-hydroxprogesterone caproate (17-P) for preterm birth prevention is unknown. The objectives of our study were to 1) examine the racial and ethnic representation of participants in 17-P preterm birth prevention studies, 2) evaluate adherence to the NIH race and ethnicity reporting guidelines and 3) compare racial and ethnic representation in research studies to national preterm birth incidence. METHODS: We systematically reviewed US studies published between January 2000 and December 2019. Study participant's race and ethnicity were reported using descriptive statistics then compared to US 2017//2018 preterm birth data using Pearson's chi-square. RESULTS: Eighteen studies met the inclusion criteria, 17 studies reported race, 11 studies reported ethnicity, and yet none of the studies followed the NIH criteria. Compared to 2017/2018 US preterm births, the proportion of black/African American study participants was significantly higher whereas the proportions of all other race categories were lower. CONCLUSIONS: More detailed reporting of race and ethnicity is needed in 17-P literature. Black women appear to be well represented while other racial and ethnic groups may be understudied.


Subject(s)
Ethnicity , Premature Birth , 17 alpha-Hydroxyprogesterone Caproate , 17-alpha-Hydroxyprogesterone , Caproates , Female , Humans , Infant, Newborn , Premature Birth/epidemiology , Premature Birth/etiology , Premature Birth/prevention & control
9.
PLoS One ; 17(8): e0272155, 2022.
Article in English | MEDLINE | ID: mdl-36006907

ABSTRACT

BACKGROUND: Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research. STUDY DESIGN: Pregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks' gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3). RESULTS: A total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging. CONCLUSION: We demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.


Subject(s)
Premature Birth , Cohort Studies , Female , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Longitudinal Studies , Pregnancy , Premature Birth/prevention & control , Prospective Studies
10.
BMJ Open ; 12(8): e064049, 2022 08 24.
Article in English | MEDLINE | ID: mdl-36002221

ABSTRACT

INTRODUCTION: Vaginal progesterone and a cervical pessary are both interventions that are investigated for the prevention of preterm birth (PTB). Thus far, beneficial or harmful effects of these interventions on long-term child health and development are described, but evidence is not robust enough to draw firm conclusions. With this follow-up study, we intent to investigate if progesterone or a pessary is superior for the prevention of PTB considering the child's health at 4-6 years of corrected age. METHODS AND ANALYSIS: This study is a follow-up study of the Quadruple-P trial; a multicentre, randomised clinical trial (NL42926.018.13, Eudractnumber 2013-002884-24) which randomises women with an asymptomatic midtrimester short cervix to daily progesterone or a pessary for the prevention of PTB. All children born to mothers who participated in the Quadruple-P study (n=628 singletons and n=332 multiples) will be eligible for follow-up at 4-6 years of corrected age. Children will be assessed using parental questionnaires. Main outcomes are child (neuro)development and behaviour. Other outcomes include child mortality, growth and general health. A composite of adverse child outcomes will be compared between the progesterone and pessary groups reporting OR and the corresponding 95% CI. Analyses will be performed separately for singletons and multiples and using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (WMO) did not apply to our study (W20_481 #20.531). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NL9646).


Subject(s)
Pessaries , Premature Birth , Cervical Length Measurement , Cervix Uteri/diagnostic imaging , Child , Female , Follow-Up Studies , Humans , Infant, Newborn , Multicenter Studies as Topic , Pregnancy , Premature Birth/prevention & control , Progesterone/therapeutic use , Randomized Controlled Trials as Topic
11.
PLoS Med ; 19(8): e1004074, 2022 08.
Article in English | MEDLINE | ID: mdl-35998205

ABSTRACT

BACKGROUND: Preterm birth-related complications are the leading cause of death in newborns and children under 5. Health outcomes of preterm newborns can be improved with appropriate use of antenatal corticosteroids (ACSs) to promote fetal lung maturity, tocolytics to delay birth, magnesium sulphate for fetal neuroprotection, and antibiotics for preterm prelabour rupture of membranes. However, there are wide disparities in the rate and consistency in the use of these interventions across settings, which may underlie the differential health outcomes among preterm newborns. We aimed to assess factors (barriers and facilitators) affecting the appropriate use of ACS, tocolytics, magnesium sulphate, and antibiotics to improve preterm birth management. METHODS AND FINDINGS: We conducted a mixed-methods systematic review including primary qualitative, quantitative, and mixed-methods studies. We searched MEDLINE, EMBASE, CINAHL, Global Health, and grey literature from inception to 16 May 2022. Eligible studies explored perspectives of women, partners, or community members who experienced preterm birth or were at risk of preterm birth and/or received any of the 4 interventions, health workers providing maternity and newborn care, and other stakeholders involved in maternal care (e.g., facility managers, policymakers). We used an iterative narrative synthesis approach to analysis, assessed methodological limitations using the Mixed Methods Appraisal Tool, and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. Behaviour change models (Theoretical Domains Framework; Capability, Opportunity, and Motivation (COM-B)) were used to map barriers and facilitators affecting appropriate use of these interventions. We included 46 studies from 32 countries, describing factors affecting use of ACS (32/46 studies), tocolytics (13/46 studies), magnesium sulphate (9/46 studies), and antibiotics (5/46 studies). We identified a range of barriers influencing appropriate use of the 4 interventions globally, which include the following: inaccurate gestational age assessment, inconsistent guidelines, varied knowledge, perceived risks and benefits, perceived uncertainties and constraints in administration, confusion around prescribing and administering authority, and inadequate stock, human resources, and labour and newborn care. Women reported hesitancy in accepting interventions, as they typically learned about them during emergencies. Most included studies were from high-income countries (37/46 studies), which may affect the transferability of these findings to low- or middle-income settings. CONCLUSIONS: In this study, we identified critical factors affecting implementation of 4 interventions to improve preterm birth management globally. Policymakers and implementers can consider these barriers and facilitators when formulating policies and planning implementation or scale-up of these interventions. Study findings can inform clinical preterm birth guidelines and implementation to ensure that barriers are addressed, and enablers are reinforced to ensure these interventions are widely available and appropriately used globally.


Subject(s)
Premature Birth , Tocolytic Agents , Anti-Bacterial Agents , Female , Humans , Infant, Newborn , Magnesium Sulfate/therapeutic use , Parturition , Pregnancy , Premature Birth/prevention & control
13.
Lancet ; 400(10352): 592-604, 2022 08 20.
Article in English | MEDLINE | ID: mdl-35988568

ABSTRACT

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.


Subject(s)
Infant, Premature, Diseases , Premature Birth , Respiratory Distress Syndrome, Newborn , Betamethasone , Double-Blind Method , Female , Humans , Infant, Newborn , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Respiratory Distress Syndrome, Newborn/prevention & control
14.
Harefuah ; 161(8): 500-505, 2022 Aug.
Article in Hebrew | MEDLINE | ID: mdl-35979569

ABSTRACT

INTRODUCTION: Preterm labor involves about 7.4% of live births in Israel and constitutes over 85% of morbidity and mortality in newborns. Risk factors for preterm labor include a history of preterm delivery shortening of the uterine cervix, cervical procedures, uterine malformations, polyhydramnios, intrauterine growth restriction, preeclampsia, multiple gestations, and more. Progesterone is an essential hormone in the process of fertilization and is involved in the menstrual cycle, implantation and preservation of pregnancy. Due to its various functions in the prevention of preterm labor, the use of progesterone as a preventive treatment has been extensively studied since the second half of the last century and tested in various forms of administration, mainly intramuscular injection and vaginal root. For years, women with a history of preterm labor were treated with intramuscular progesterone once a week between 16 to 36 weeks' gestation or until birth. Recently, vaginal progesterone treatment was initiated in women with cervical length > 25 mm measured by ultrasound between 18-24 weeks gestation. Studies have shown that progesterone treatment reduces the incidence of preterm labor given in the proper indication. This update overview examines progesterone treatment for the prevention of preterm labor.


Subject(s)
Obstetric Labor, Premature , Premature Birth , Administration, Intravaginal , Cervix Uteri , Female , Humans , Infant, Newborn , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Pregnancy , Premature Birth/prevention & control , Progesterone
15.
BMC Pregnancy Childbirth ; 22(1): 639, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35971107

ABSTRACT

BACKGROUND: Disparities in stillbirth and preterm birth persist even after correction for ethnicity and social deprivation, demonstrating that there is wide geographical variation in the quality of care. To address this inequity, Tommy's National Centre for Maternity Improvement developed the Tommy's Clinical Decision Tool, which aims to support the provision of "the right care at the right time", personalising risk assessment and care according to best evidence. This web-based clinical decision tool assesses the risk of preterm birth and placental dysfunction more accurately than current methods, and recommends best evidenced-based care pathways in a format accessible to both women and healthcare professionals. It also provides links to reliable sources of pregnancy information for women. The aim of this study is to evaluate implementation of Tommy's Clinical Decision Tool in four early-adopter UK maternity services, to inform wider scale-up. METHODS: The Tommy's Clinical Decision Tool has been developed involving maternity service users and healthcare professionals in partnership. This mixed-methods study will evaluate: maternity service user and provider acceptability and experience; barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences. Data will be gathered over 25 months through interviews, focus groups, questionnaires and through the Tommy's Clinical Decision Tool itself. The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) will inform data analysis. DISCUSSION: This paper describes the intervention, Tommy's Clinical Decision Tool, according to TiDIER guidelines, and the protocol for the early adopter implementation evaluation study. Findings will inform future scale up. TRIAL REGISTRATION: This study was prospectively registered on the ISRCTN registry no. 13498237 , on 31st January 2022.


Subject(s)
Premature Birth , Female , Focus Groups , Health Personnel , Humans , Infant, Newborn , Placenta , Pregnancy , Premature Birth/prevention & control , Stillbirth
16.
Eur J Obstet Gynecol Reprod Biol ; 277: 1-6, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35961147

ABSTRACT

OBJECTIVES: Since late preterm neonates are physiologically less mature than term neonates, the use of antenatal corticosteroids in the late preterm period has been recommended. The use of tocolytics can also be considered to gain valuable time for using antenatal corticosteroids in the late preterm period. In this study, we examined the efficacy of tocolytics on prolonging pregnancy in the late preterm period, by comparing women who received tocolytics with those who received none. STUDY DESIGN: This retrospective cohort study included women who were admitted due to preterm labor after 34 weeks of gestation and delivered in the late preterm period. Primary outcome was time from admission to delivery (days). Secondary outcomes were the proportion of preterm births within 2 days, and within 7 days, completed cycles of antenatal corticosteroids, and the neonatal outcomes. Primary and secondary outcomes were compared according to the use of tocolytics. Propensity score matching was performed to create comparable groups. The maternal age, pre-pregnancy body mass index, nulliparity, history of preterm birth, hypertensive disease during pregnancy, gestational diabetes mellitus, history of preterm labor, gestational age at admission, cervical length, and the number of contractions were the baseline characteristics included in the propensity score. RESULTS: Of 275 women, 44 women received tocolytics (tocolytics group) and 231 women did not (no tocolytics group). We matched 44 women who received tocolytics and 44 women who didn't. The tocolytics group was shown to exhibit a longer time from admission to delivery than the no tocolytics group, with a hazard ratio for tocolytics of 0.4 (95 % confidence interval, 0.2-0.6). In addition, the proportion of preterm births occurring within 2 days and 7 days were lower in those receiving tocolytics compared to those that didn't. CONCLUSION: In this propensity score matched-study, the use of tocolytics had a significant effect on pregnancy prolongation, which allows more time for use of corticosteroids in women with preterm labor after 34 weeks of gestation.


Subject(s)
Obstetric Labor, Premature , Premature Birth , Tocolytic Agents , Female , Humans , Infant, Newborn , Obstetric Labor, Premature/drug therapy , Obstetric Labor, Premature/prevention & control , Parity , Pregnancy , Premature Birth/prevention & control , Propensity Score , Retrospective Studies , Tocolytic Agents/therapeutic use
17.
Cochrane Database Syst Rev ; 8: CD014978, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35947046

ABSTRACT

BACKGROUND: Preterm birth is the leading cause of death in newborns and children. Tocolytic drugs aim to delay preterm birth by suppressing uterine contractions to allow time for administration of corticosteroids for fetal lung maturation, magnesium sulphate for neuroprotection, and transport to a facility with appropriate neonatal care facilities. However, there is still uncertainty about their effectiveness and safety. OBJECTIVES: To estimate relative effectiveness and safety profiles for different classes of tocolytic drugs for delaying preterm birth, and provide rankings of the available drugs. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (21 April 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials assessing effectiveness or adverse effects of tocolytic drugs for delaying preterm birth. We excluded quasi- and non-randomised trials. We evaluated all studies against predefined criteria to judge their trustworthiness. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion and risk of bias, and extracted data. We performed pairwise and network meta-analyses, to determine the relative effects and rankings of all available tocolytics. We used GRADE to rate the certainty of the network meta-analysis effect estimates for each tocolytic versus placebo or no treatment. MAIN RESULTS: This network meta-analysis includes 122 trials (13,697 women) involving six tocolytic classes, combinations of tocolytics, and placebo or no treatment. Most trials included women with threatened preterm birth, singleton pregnancy, from 24 to 34 weeks of gestation. We judged 25 (20%) studies to be at low risk of bias. Overall, certainty in the evidence varied. Relative effects from network meta-analysis suggested that all tocolytics are probably effective in delaying preterm birth compared with placebo or no tocolytic treatment. Betamimetics are possibly effective in delaying preterm birth by 48 hours (risk ratio (RR) 1.12, 95% confidence interval (CI) 1.05 to 1.20; low-certainty evidence), and 7 days (RR 1.14, 95% CI 1.03 to 1.25; low-certainty evidence). COX inhibitors are possibly effective in delaying preterm birth by 48 hours (RR 1.11, 95% CI 1.01 to 1.23; low-certainty evidence). Calcium channel blockers are possibly effective in delaying preterm birth by 48 hours (RR 1.16, 95% CI 1.07 to 1.24; low-certainty evidence), probably effective in delaying preterm birth by 7 days (RR 1.15, 95% CI 1.04 to 1.27; moderate-certainty evidence), and prolong pregnancy by 5 days (0.1 more to 9.2 more; high-certainty evidence). Magnesium sulphate is probably effective in delaying preterm birth by 48 hours (RR 1.12, 95% CI 1.02 to 1.23; moderate-certainty evidence). Oxytocin receptor antagonists are probably effective in delaying preterm birth by 48 hours (RR 1.13, 95% CI 1.05 to 1.22; moderate-certainty evidence), are effective in delaying preterm birth by 7 days (RR 1.18, 95% CI 1.07 to 1.30; high-certainty evidence), and possibly prolong pregnancy by 10 days (95% CI 2.3 more to 16.7 more). Nitric oxide donors are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.05 to 1.31; moderate-certainty evidence), and 7 days (RR 1.18, 95% CI 1.02 to 1.37; moderate-certainty evidence). Combinations of tocolytics are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.07 to 1.27; moderate-certainty evidence), and 7 days (RR 1.19, 95% CI 1.05 to 1.34; moderate-certainty evidence). Nitric oxide donors ranked highest for delaying preterm birth by 48 hours and 7 days, and delay in birth (continuous outcome), followed by calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics. Betamimetics (RR 14.4, 95% CI 6.11 to 34.1; moderate-certainty evidence), calcium channel blockers (RR 2.96, 95% CI 1.23 to 7.11; moderate-certainty evidence), magnesium sulphate (RR 3.90, 95% CI 1.09 to 13.93; moderate-certainty evidence) and combinations of tocolytics (RR 6.87, 95% CI 2.08 to 22.7; low-certainty evidence) are probably more likely to result in cessation of treatment. Calcium channel blockers possibly reduce the risk of neurodevelopmental morbidity (RR 0.51, 95% CI 0.30 to 0.85; low-certainty evidence), and respiratory morbidity (RR 0.68, 95% CI 0.53 to 0.88; low-certainty evidence), and result in fewer neonates with birthweight less than 2000 g (RR 0.49, 95% CI 0.28 to 0.87; low-certainty evidence). Nitric oxide donors possibly result in neonates with higher birthweight (mean difference (MD) 425.53 g more, 95% CI 224.32 more to 626.74 more; low-certainty evidence), fewer neonates with birthweight less than 2500 g (RR 0.40, 95% CI 0.24 to 0.69; low-certainty evidence), and more advanced gestational age (MD 1.35 weeks more, 95% CI 0.37 more to 2.32 more; low-certainty evidence). Combinations of tocolytics possibly result in fewer neonates with birthweight less than 2500 g (RR 0.74, 95% CI 0.59 to 0.93; low-certainty evidence). In terms of maternal adverse effects, betamimetics probably cause dyspnoea (RR 12.09, 95% CI 4.66 to 31.39; moderate-certainty evidence), palpitations (RR 7.39, 95% CI 3.83 to 14.24; moderate-certainty evidence), vomiting (RR 1.91, 95% CI 1.25 to 2.91; moderate-certainty evidence), possibly headache (RR 1.91, 95% CI 1.07 to 3.42; low-certainty evidence) and tachycardia (RR 3.01, 95% CI 1.17 to 7.71; low-certainty evidence) compared with placebo or no treatment. COX inhibitors possibly cause vomiting (RR 2.54, 95% CI 1.18 to 5.48; low-certainty evidence). Calcium channel blockers (RR 2.59, 95% CI 1.39 to 4.83; low-certainty evidence), and nitric oxide donors probably cause headache (RR 4.20, 95% CI 2.13 to 8.25; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo or no tocolytic treatment, all tocolytic drug classes that we assessed (betamimetics, calcium channel blockers, magnesium sulphate, oxytocin receptor antagonists, nitric oxide donors) and their combinations were probably or possibly effective in delaying preterm birth for 48 hours, and 7 days. Tocolytic drugs were associated with a range of adverse effects (from minor to potentially severe) compared with placebo or no tocolytic treatment, although betamimetics and combination tocolytics were more likely to result in cessation of treatment. The effects of tocolytic use on neonatal outcomes such as neonatal and perinatal mortality, and on safety outcomes such as maternal and neonatal infection were uncertain.


Subject(s)
Premature Birth , Tocolytic Agents , Adrenergic beta-Agonists , Birth Weight , Calcium Channel Blockers/therapeutic use , Child , Female , Headache , Humans , Infant, Newborn , Magnesium Sulfate/therapeutic use , Network Meta-Analysis , Nitric Oxide Donors/therapeutic use , Pregnancy , Premature Birth/prevention & control , Randomized Controlled Trials as Topic , Receptors, Oxytocin , Tocolytic Agents/adverse effects , Tocolytic Agents/therapeutic use , Vomiting/drug therapy
18.
BMJ Glob Health ; 7(8)2022 08.
Article in English | MEDLINE | ID: mdl-35948345

ABSTRACT

BACKGROUND: Low birth weight (LBW), including preterm birth (PTB) and small for gestational age (SGA), contributes a significant global health burden. We aimed to summarise current evidence on the effect of preconception and periconception interventions on LBW, SGA and PTB. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library and WHO Global Index Medicus for randomised controlled trials and quasi-experimental studies published by 28 November 2020, which assessed interventions delivered in preconception and periconception or preconception and pregnancy. Primary outcomes were LBW, SGA and PTB. Studies were categorised by intervention type and delivery during preconception and periconception or during preconception and pregnancy. Estimates were pooled using fixed-effects or random-effects restricted maximum likelihood method meta-analyses. Quality of evidence for primary outcomes was assessed using the Grades of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We included 58 studies. Twenty-eight studies examined nutrition interventions (primarily micronutrient or food supplementation). Thirty studies (including one reporting a nutrition intervention) provided health interventions (general preconception health, early adverse pregnancy outcome prevention, non-communicable disease and infectious disease prevention and management). One study assessed a social intervention (reproductive planning). Studies varied in terms of specific interventions, including delivery across preconception or pregnancy, resulting in few studies for any single comparison. Overall, the evidence was generally very uncertain regarding the impact of any intervention on LBW, SGA and PTB. Additionally, preconception and periconception nutritional supplementation containing folic acid was associated with reduced risk of birth defects (10 studies, N=3 13 312, risk ratio: 0.37 (95% CI: 0.24 to 0.55), I2: 74.33%). CONCLUSION: We found a paucity of evidence regarding the impact of preconception and periconception interventions on LBW, SGA and PTB. Further research on a wider range of interventions is required to clearly ascertain their potential effectiveness. TRIAL REGISTRATION NUMBER: This review was prospectively registered with PROSPERO (CRD42020220915).


Subject(s)
Premature Birth , Female , Folic Acid , Gestational Age , Humans , Infant, Low Birth Weight , Infant, Newborn , Micronutrients , Pregnancy , Premature Birth/chemically induced , Premature Birth/prevention & control
19.
Cochrane Database Syst Rev ; 8: CD006764, 2022 08 09.
Article in English | MEDLINE | ID: mdl-35943347

ABSTRACT

BACKGROUND: Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type of corticosteroid to use, dose, frequency, timing of use or the route of administration.  OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal morbidity and mortality, and on the child and adult in later life, of administering different types of corticosteroids (dexamethasone or betamethasone), or different corticosteroid dose regimens, including timing, frequency and mode of administration. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 May 2022) and reference lists of retrieved studies. SELECTION CRITERIA: We included all identified published and unpublished randomised controlled trials or quasi-randomised controlled trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth. We planned to exclude cross-over trials and cluster-randomised trials. We planned to include studies published as abstracts only along with studies published as full-text manuscripts. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 11 trials (2494 women and 2762 infants) in this update, all of which recruited women who were at increased risk of preterm birth or had a medical indication for preterm birth. All trials were conducted in high-income countries. Dexamethasone versus betamethasone Nine trials (2096 women and 2319 infants) compared dexamethasone versus betamethasone. All trials administered both drugs intramuscularly, and the total dose in the course was consistent (22.8 mg or 24 mg), but the regimen varied. We assessed one new study to have no serious risk of bias concerns for most outcomes, but other studies were at moderate (six trials) or high (two trials) risk of bias due to selection, detection and attrition bias. Our GRADE assessments ranged between high- and low-certainty, with downgrades due to risk of bias and imprecision.  Maternal outcomes The only maternal primary outcome reported was chorioamnionitis (death and puerperal sepsis were not reported). Although the rate of chorioamnionitis was lower with dexamethasone, we did not find conclusive evidence of a difference between the two drugs (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.48 to 1.06; 1 trial, 1346 women; moderate-certainty evidence). The proportion of women experiencing maternal adverse effects of therapy was lower with dexamethasone; however, there was not conclusive evidence of a difference between interventions (RR 0.63, 95% CI 0.35 to 1.13; 2 trials, 1705 women; moderate-certainty evidence). Infant outcomes We are unsure whether the choice of drug makes a difference to the risk of any known death after randomisation, because the 95% CI was compatible with both appreciable benefit and harm with dexamethasone (RR 1.03, 95% CI 0.66 to 1.63; 5 trials, 2105 infants; moderate-certainty evidence). The choice of drug may make little or no difference to the risk of RDS (RR 1.06, 95% CI 0.91 to 1.22; 5 trials, 2105 infants; high-certainty evidence). While there may be little or no difference in the risk of intraventricular haemorrhage (IVH), there was substantial unexplained statistical heterogeneity in this result (average (a) RR 0.71, 95% CI 0.28 to 1.81; 4 trials, 1902 infants; I² = 62%; low-certainty evidence). We found no evidence of a difference between the two drugs for chronic lung disease (RR 0.92, 95% CI 0.64 to 1.34; 1 trial, 1509 infants; moderate-certainty evidence), and we are unsure of the effects on necrotising enterocolitis, because there were few events in the studies reporting this outcome (RR 5.08, 95% CI 0.25 to 105.15; 2 studies, 441 infants; low-certainty evidence). Longer-term child outcomes Only one trial consistently followed up children longer term, reporting  at two years' adjusted age. There is probably little or no difference between dexamethasone and betamethasone in the risk of neurodevelopmental disability at follow-up (RR 1.02, 95% CI 0.85 to 1.22; 2 trials, 1151 infants; moderate-certainty evidence). It is unclear whether the choice of drug makes a difference to the risk of visual impairment (RR 0.33, 95% CI 0.01 to 8.15; 1 trial, 1227 children; low-certainty evidence). There may be little or no difference between the drugs for hearing impairment (RR 1.16, 95% CI 0.63 to 2.16; 1 trial, 1227 children; moderate-certainty evidence), motor developmental delay (RR 0.89, 95% CI 0.66 to 1.20; 1 trial, 1166 children; moderate-certainty evidence) or intellectual impairment (RR 0.97, 95% CI 0.79 to 1.20; 1 trial, 1161 children; moderate-certainty evidence). However, the effect estimate for cerebral palsy is compatible with both an important increase in risk with dexamethasone, and no difference between interventions (RR 2.50, 95% CI 0.97 to 6.39; 1 trial, 1223 children; low-certainty evidence). No trials followed the children beyond early childhood. Comparisons of different preparations and regimens of corticosteroids We found three studies that included a comparison of a different regimen or preparation of either dexamethasone or betamethasone (oral dexamethasone 32 mg versus intramuscular dexamethasone 24 mg; betamethasone acetate plus phosphate versus betamethasone phosphate; 12-hourly betamethasone versus 24-hourly betamethasone). The certainty of the evidence for the main outcomes from all three studies was very low, due to  small sample size and  risk of bias. Therefore, we were limited in our ability to draw conclusions from any of these studies. AUTHORS' CONCLUSIONS: Overall, it remains unclear whether there are important differences between dexamethasone and betamethasone, or between one regimen and another.  Most trials compared dexamethasone versus betamethasone. While for most infant and early childhood outcomes there may be no difference between these drugs, for several important outcomes for the mother, infant and child the evidence was inconclusive and did not rule out significant benefits or harms. The evidence on different antenatal corticosteroid regimens was sparse, and does not support the use of one particular corticosteroid regimen over another.


Subject(s)
Chorioamnionitis , Premature Birth , Respiratory Distress Syndrome, Newborn , Adrenal Cortex Hormones , Betamethasone/adverse effects , Child , Child, Preschool , Dexamethasone/adverse effects , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Lung , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Respiratory Distress Syndrome, Newborn/prevention & control
20.
BMJ Open Qual ; 11(3)2022 08.
Article in English | MEDLINE | ID: mdl-35944934

ABSTRACT

Perinatal Excellence to Reduce Injury in Premature Birth (PERIPrem) is an 11-element perinatal care bundle designed to improve outcomes for preterm babies, in line with the National Health Service (NHS) Long Term plan. Designed in collaboration with 12 NHS Trusts (secondary care hospitals), South West and West of England Academic Health Science Networks, South West Neonatal Operational Delivery Network, parent partners and clinical experts, implementation was via bespoke quality improvement (QI) methodology. Before project initiation, there was regional variation in uptake of elements, evidenced by baseline audit. Optimisation of the preterm infant is complex; eligibility for treatments is dependent on gestation and local policies. Preterm infants experience variability in care dependent on the place of birth, and there remains an implementation gap for several effective, evidence-based treatments.The PERIPrem ambition is to reduce severe brain injury and death caused by prematurity by at least 50% through the delivery of a perinatal care bundle. The PERIPrem approach resulted in improved element implementation by 26% (from 3% to 29%) between 2019 and 2021, with dyads significantly more likely to receive the full bundle in 2021 compared with 2019 (probability=0.96 (95% CI 0.87 to 0.99), p<0.001). When examining the impact on psychological safety and team-working of PERIPrem, linear mixed models indicated an improvement in team function (p=0.021), situation monitoring (p=0.029) and communication within teams (p=0.002). Central to success was the development of a committed multiorganisational collaborative that continues to drive perinatal improvement using a common language and streamlining processes. In addition to saving the lives of the most vulnerable babies, PERIPrem aims to improve the chances of disability-free lives and is successfully nurturing high-functioning perinatal teams with enhanced QI skills.


Subject(s)
Premature Birth , England , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Pregnancy , Premature Birth/epidemiology , Premature Birth/prevention & control , Quality Improvement , State Medicine
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