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Low-dose aspirin and preterm birth: a randomized controlled trial.

ABSTRACT: OBJECTIVE:To evaluate the association between low-dose aspirin initiated before conception and the risk of preterm birth. METHODS:This was a secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial. Women with a history of pregnancy loss (original stratum: one loss less than 20 weeks of gestation during the previous year; expanded stratum: one or two losses with no restrictions on timing or gestational age of the losses) were randomized to either daily low-dose aspirin (81 mg, n=615) and folic acid or folic acid alone (placebo; n=613). Preterm birth was compared between groups using intent-to-treat analysis. RESULTS:Preterm birth rates were 4.1% (22/535 low-dose aspirin) and 5.7% (31/543 placebo) (relative risk [RR] 0.72, 95% confidence interval [CI] 0.42-1.23); spontaneous preterm birth rates were 1.1% (6/535 low-dose aspirin) and 2.2% (12/543 placebo) (RR 0.51, 95% CI 0.19-1.34); medically indicated preterm birth rates were 2.6% (14/535 low-dose aspirin) and 2.9% (16/543 placebo) (RR 0.89, 95% CI 0.44-1.80). After restriction to confirmed pregnancies using inverse probability weighting, preterm birth rates were 5.7% and 9.0% (RR 0.63, 95% CI 0.37-1.09) and spontaneous preterm birth rates were 1.4% and 3.2% (RR 0.44, 95% CI 0.17-1.18). In confirmed pregnancies in the original stratum, preterm birth occurred in 3.8% and 9.7% of the low-dose aspirin and placebo groups, respectively (RR 0.39, 95% CI 0.16-0.94). CONCLUSION:Preconception low-dose aspirin was not significantly associated with the overall rate of preterm birth. Although the study was underpowered for this secondary analysis, numeric trends in favor of benefit, particularly in the women with a recent, single early pregnancy loss, warrant further investigation. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, www.clinicaltrials.gov, NCT00467363.

SUBMITTER: Silver RM

PROVIDER: S-EPMC6152923 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Low-dose aspirin and preterm birth: a randomized controlled trial.

Silver Robert M RM Ahrens Katherine K Wong Luchin F LF Perkins Neil J NJ Galai Noya N Lesher Laurie L LL Faraggi David D Wactawski-Wende Jean J Townsend Janet M JM Lynch Anne M AM Mumford Sunni L SL Sjaarda Lindsey L Schisterman Enrique F EF

Obstetrics and gynecology 20150401 4

<h4>Objective</h4>To evaluate the association between low-dose aspirin initiated before conception and the risk of preterm birth.<h4>Methods</h4>This was a secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial. Women with a history of pregnancy loss (original stratum: one loss less than 20 weeks of gestation during the previous year; expanded stratum: one or two losses with no restrictions on timing or gestational age of the losses) were randomized to either daily low- ...[more]

PMID: 25751215

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Project description:Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial.Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA)?<?37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo.This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth.Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Project description:What is the association between daily preconception-initiated low-dose aspirin (LDA) treatment and very early pregnancy losses or euploid (chromosomally normal) losses among women with one to two prior losses?Daily LDA initiated preconception was not associated with the rate or type of pregnancy loss among women with a history of one to two prior pregnancy losses.LDA is often used to treat recurrent pregnancy loss with reductions in pregnancy loss generally only observed among women with antiphospholipid antibodies, and null associations observed among women without antiphospholipid antibodies. We previously evaluated the association between LDA and pregnancy loss overall among women with one to two prior losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and found no association, though did not distinguish between potential effects at different stages of pregnancy loss, including implantation failure, or between euploid and aneuploid losses.The EAGeR trial was a multi-site prospective block-randomized double-blind placebo-controlled trial. In total, 1228 women were randomized to daily LDA (81 mg/day) plus folic acid (400 mcg/day), or placebo plus folic acid. Participants were assigned study drug for less than or equal to six menstrual cycles or if they conceived, throughout pregnancy with study drug discontinued at 36 weeks gestation. This analysis includes additional outcome information obtained from chart abstractions after the completion of the trial, as well as testing of stored urine for measurement of hCG and detection of very early pregnancy losses, and karyotyping of the products of conception for assessment of aneuploidy of the losses.Women aged 18-40 with a history of one to two prior losses and actively trying to conceive were randomized (n = 615 LDA and n = 613 placebo) at four clinical centers in the USA (2007-2011). Log-binomial regression was used to estimate risk ratios under the intent-to-treat approach.Daily LDA initiated preconception was not associated with clinically recognized pregnancy losses or implantation failures among women with proved fecundity and a history of one to two prior losses. Specifically, 1088 (88.6%) women completed the trial with 797 having an hCG detected pregnancy (64.9%). Overall there were 133 clinical losses (12.7% LDA versus 11.8% placebo, P = 0.71) and 55 implantation failures (5.2% LDA versus 4.9% placebo, P = 0.89). No differences were found in rate of euploid losses (RR 1.11, 95% confidence interval: 0.99, 1.26).Generalizability of these findings is limited to women with a history of one to two prior losses, and may further be limited to women of white race with higher socioeconomic status as given the rigors of the study protocol participants tended to be white and have higher incomes and more education. We were also missing karyotype information on approximately one-third of the clinically recognized pregnancy losses, which may limit our power to detect effects on euploid losses, though detailed sensitivity analysis showed similar results.Our data do not support the general use of LDA to decrease pregnancy loss and further demonstrate no increased risk of loss for women on LDA treatment.This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). The authors have no conflicts of interest.The trial was registered at ClinicalTrials.gov #NCT00467363.27 April 2007.15 June 2007.

Project description:BackgroundPreterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.MethodsASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.FindingsFrom March 23, 2016 to June 30, 2018, 14?361 women were screened for inclusion and 11?976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.InterpretationIn populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development.

Project description:Preterm birth (PTB) is a leading cause of infant morbidity and mortality worldwide. Every year, 20 million babies are born with low birthweight (LBW), about 96% of which occur in low-income countries. Despite the associated dangers, in about 40%-50% of PTB and LBW cases, the causes remain unexplained. Existing evidence is inconclusive as to whether occupational physical activities such as heavy lifting are implicated. African women bear the transport burden of accessing basic needs for their families. Ghana's PTB rate is 14.5%, whereas the global average is 9.6%. The proposed liftless intervention aims to decrease lifting exposure during pregnancy among Ghanaian women. We hypothesize that a reduction in heavy lifting among pregnant women in Ghana will increase gestational age and birthweight.To investigate the effects of the liftless intervention on the incidence of PTB and LBW among pregnant Ghanaian women.A cohort stepped-wedge cluster randomized controlled trial in 10 antenatal clinics will be carried out in Ghana. A total of 1000 pregnant participants will be recruited for a 60-week period. To be eligible, the participant should have a singleton pregnancy between 12 and 16 weeks gestation, be attending any of the 10 antenatal clinics, and be exposed to heavy lifting. All participants will receive standard antenatal care within the control phase; by random allocation, two clusters will transit into the intervention phase. The midwife-led 3-component liftless intervention consists of health education, a take-home reminder card mimicking the colors of a traffic light, and a shopping voucher. The primary outcome are gestational ages of <28, 28-32, and 33-37 weeks. The secondary outcomes are LBW (preterm LBW, term but LBW, and postterm), compliance, prevalence of low back and pelvic pain, and premature uterine contractions. Study midwives and participants will not be blinded to the treatment allocation.Permission to conduct the study at all 10 antenatal clinics has been granted by the Ghana Health Service. Application for funding to begin the trial is ongoing. Findings from the main trial are expected to be published by the end of 2019.To the best of our knowledge, there has been no randomized trial of this nature in Ghana. Minimizing heavy lifting among pregnant African women can reduce the soaring rates of PTB and LBW. The findings will increase the knowledge of the prevention of PTB and LBW worldwide.Pan African Clinical Trial Register (PACTR201602001301205); http://apps.who.int/trialsearch/ Trial2.aspx?TrialID=PACTR201602001301205 (Archived by WebCite at http://www.webcitation.org/71TCYkHzu).RR1-10.2196/10095.

Project description:BackgroundSystemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants.MethodsA prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented.ResultsA total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period.ConclusionsNystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups.Trial registrationNCT03390374. Registered 4 January 2018 - Retrospectively registered.

Project description:BackgroundLow-dose aspirin (LDA) has been proposed as a safe and inexpensive prophylactic agent. Studies in European/Western populations have shown promising results indicating that LDA can reduce the occurrence of pre-eclampsia (PE) in women with identifiable risk factors. However, few controlled trials, particularly large randomized controlled trials, have been performed in Asian populations. The aim of this project is to evaluate the effect of LDA for PE prevention on high-risk pregnant women in China, where PE is highly prevalent and the LDA supply status is commonly suboptimal.Methods/designAn open-label, multicentre randomized controlled trial is being conducted at 13 tertiary hospitals in 11 provinces in China. A total of 1000 eligible women with high-risk factors for developing PE according to their medical histories are being randomized into two groups: a control group (n = 500) and an intervention group (n = 500). Women with high-risk factors, such as a history of PE, chronic hypertension, type 1 or 2 diabetes, advanced maternal age, obesity, family history of PE or nulliparity are eligible. The control group is advised to undergo routine examinations, whereas the intervention group undergoes the routine examinations and receives LDA. LDA (100 mg/d) should be prescribed at night, initiating from early pregnancy (12-20 weeks of gestation) and lasting until 34 weeks of gestation. Demographic data and clinical endpoint outcomes, as well as biological samples (e.g., maternal blood, cord blood, amniotic fluid and placental samples), will be collected. The primary outcome is the occurrence of PE, and the secondary outcomes include maternal and neonatal outcomes and maternal biomarker levels.DiscussionThis is the first and largest multicentre randomized controlled trial to assess the effect of LDA in preventing PE in a Chinese population. The results will potentially influence the prenatal care recommendations in China regarding intervention with LDA for PE.Trial registrationClinicalTrials.gov, NCT02797249 . Registered on 7 June 2016.

Project description:Low socioeconomic status (SES) is associated with adverse pregnancy outcomes and infertility. Low-dose aspirin (LDA) was shown to improve livebirth rates in certain subsets of women, and therefore, may impact pregnancy rates differentially by SES status. Therefore, the aim of the current study was to examine whether daily preconception-initiated LDA affects rates of pregnancy, livebirth, and pregnancy loss differently across strata of socioeconomic status (SES). This is a secondary analysis of The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial, a multisite, block- randomized, placebo-controlled trial conducted at four U.S. medical centers (n = 1,228, 2007-2012). Women attempting spontaneous conception with a history of pregnancy loss were randomly allocated preconception to 81mg of aspirin + 400mcg of folic acid (n = 615) or placebo + 400mcg of folic acid (n = 613). Study medication was administered for six menstrual cycles or until 36 weeks' gestation if pregnancy was achieved. For this analysis, women were stratified by SES, which included income (low, mid, high) and a combined grouping of education and income (low-low, low-high, high-low, high-high). Log binomial models with robust variance estimated risks of pregnancy, livebirth, and pregnancy loss for LDA versus placebo. LDA increased pregnancy and livebirth rates (RR 1.23, 95% CI: 1.03, 1.45) in the high-income, but not mid- or low-income groups. LDA increased pregnancy rates in both the low education-low income group (RR 1.22, 95% CI: 1.02, 1.46) and the high education-high income group (RR 1.23, 95%CI: 1.06, 1.42), with no effect observed in mid-SES groupings. LDA, a low-cost and widely available treatment, may be particularly beneficial to women at the highest and lowest ends of the socioeconomic spectrum, though underlying mechanisms of this disparity are unclear. Confirming these findings and identifying factors which may modulate the effectiveness of LDA will ultimately facilitate personalized clinical care and improvements in population-level reproductive health. Trial registration number: ClinicalTrials.gov, NCT00467363.

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Low-dose aspirin and preterm birth: a randomized controlled trial.

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Low-dose aspirin and preterm birth: a randomized controlled trial.

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