Dataset Information

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

ABSTRACT:

Importance

Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy.

Objective

To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia.

Design, setting, and participants

Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants.

Interventions

Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group).

Main outcomes and measures

Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%.

Results

Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority.

Conclusions and relevance

Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio.

Trial registration

ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

SUBMITTER: Mendoza M

PROVIDER: S-EPMC9945069 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

Mendoza Manel M Bonacina Erika E Garcia-Manau Pablo P López Monica M Caamiña Sara S Vives Àngels À Lopez-Quesada Eva E Ricart Marta M Maroto Anna A de Mingo Laura L Pintado Elena E Ferrer-Costa Roser R Martin Lourdes L Rodríguez-Zurita Alicia A Garcia Esperanza E Pallarols Mar M Vidal-Sagnier Laia L Teixidor Mireia M Orizales-Lago Carmen C Pérez-Gomez Adela A Ocaña Vanesa V Puerto Linda L Millán Pilar P Alsius Mercè M Diaz Sonia S Maiz Nerea N Carreras Elena E Suy Anna A

JAMA 20230201 7

<h4>Importance</h4>Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy.<h4>Objective</h4>To determine whether aspirin discontinuation in pregnant individual ...[more]

PMID: 36809321

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Project description:IntroductionThis study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation.Material and methodsThis is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups.ResultsAmong the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82).ConclusionsDiscontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.

Project description:ObjectiveWe sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision.Study designTrained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery.ResultsOf 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29-5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77-3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68-7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95-1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48-5.07).ConclusionThe risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

Project description:BackgroundShortened cervical length is one of the primary predictors for spontaneous preterm deliveries in twin pregnancies. However, there is lack of consensus regarding cut-off values. Recent evidence highlights that established cut-offs for cervical length screening might not always apply across different populations. This study aims to present the distribution of cervical length in Taiwanese twin pregnancies and to assess its predictive value for spontaneous preterm birth during mid-trimester screening.Materials and methodsThis retrospective analysis of cervical length screening in Taiwan evaluated 469 twin pregnancies between 20-24 weeks of gestation. Outcome data were obtained directly from the medical records of the delivery hospital. The study explored the predictive value of cervical length screening for spontaneous preterm birth and the characteristics of cervical length distribution in Taiwanese twin pregnancies.ResultsThe average gestational age at screening was 22.7 weeks. Cervical length values displayed a non-normal distribution (p-value <0.001). The median, 5th and 95th centiles were 37.5 mm 25.1 mm, and 47.9 mm, respectively. Various cut-off values were assessed using different methods, yielding positive [negative] likelihood ratios for spontaneous preterm births between 32-37 weeks of gestational age (GA) (1.3-30.1 and [0.51-0.92]) and for very preterm births between 28-32 weeks GA (5.6-51.1 and [0.45-0.64]).ConclusionsThe findings from our analysis of Taiwanese twin pregnancies uphold the moderate predictive potential of cervical length screening, consistent with prior investigations. The presented likelihood ratios for predicting preterm birth at different gestational ages equip clinicians with valuable tools to enhance their diagnostic rationale and resource utilization. By fine-tuning screening parameters according to the spontaneous preterm birth prevalence and clinical priorities of the particular population, healthcare providers can enhance patient care. Our data implies that a cervical length below 20 mm might provide an optimal balance between minimizing false negatives and managing false positives when predicting spontaneous preterm birth.

Project description:BackgroundPreterm labour, between 24 to 28 weeks of gestation, remains prevalent in low resource settings. There is evidence of improved survival after 24 weeks though the ideal mode of delivery remains unclear. There are no clear management protocols to guide patient management. We sought to determine the incidence of preterm labour occurring between 24 to 28 weeks, its associated risk factors and the preferred mode of delivery in a low resource setting with the aim of streamlining patient care.MethodsBetween February 2020 and September 2020, we prospectively followed 392 women with preterm labour between 24 to 28 weeks of gestation and their newborns from admission to discharge at Kawempe National Referral hospital in Kampala, Uganda. The primary outcome was perinatal mortality associated with the different modes of delivery. Secondary outcomes included neonatal and maternal infections, admission to the Neonatal Special Care Unit (SCU), need for neonatal resuscitation, preterm birth and maternal death. Chi-square test was used to assess the association between perinatal mortality and categorical variables such as parity, mode of delivery, employment status, age, antepartum hemorrhage, digital vaginal examination, and admission to Special Care unit. Multivariate logistic regression was used to assess the association between comparative outcomes of the different modes of delivery and maternal and neonatal risk factors.ResultsThe incidence of preterm labour among women who delivered preterm babies between 24 to 28 weeks was 68.9% 95% CI 64.2-73.4). Preterm deliveries between 24 to 28 weeks contributed 20% of the all preterm deliveries and 2.5% of the total hospital deliveries. Preterm labour was independently associated with gravidity (p-value = 0.038), whether labour was medically induced (p-value <0.001), number of digital examinations (p-value <0.001), history of vaginal bleeding prior to onset of labour (p-value < 0.001), whether tocolytics were given (p-value < 0.001), whether an obstetric ultrasound scan was done (p-value <0.001 and number of babies carried (p-value < 0.001). At multivariate analysis; multiple pregnancy OR 15.45 (2.00-119.53), p-value < 0.001, presence of fever prior to admission OR 4.03 (95% CI .23-13.23), p-value = 0.002 and duration of drainage of liquor OR 0.16 (0.03-0.87), p-value = 0.034 were independently associated with preterm labour. The perinatal mortality rate in our study was 778 per 1000 live births. Of the 392 participants, 359 (91.5%), had vaginal delivery, 29 (7.3%) underwent Caesarean delivery and 4 (1%) had assisted vaginal delivery. Caesarean delivery was protective against perinatal mortality compared to vaginal delivery OR = 0.36, 95% CI 0.14-0.82, p-value = 0.017). The other protective factors included receiving antenatal corticosteroids OR = 0.57, 95% CI 0.33-0.98, p-value = 0.040, Doing 3-4 digital exams per day, OR = 0.41, 95% 0.18-0.91, p-value = 0.028) and hospital stay of > 7 days, p value = 0.001. Vaginal delivery was associated with maternal infections, postpartum hemorrhage, and admission to the Special Care Unit.ConclusionCaesarean delivery is the preferred mode of delivery for preterm deliveries between 24 to 28 weeks of gestation especially when labour is not established in low resource settings. It is associated with lesser adverse pregnancy outcomes when compared to vaginal delivery for remote gestation ages.

Project description:It is now recognized that preterm infants ?28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2???0.30 at an age ?6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2???0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation.Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

Project description:IntroductionThere is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management.Material and methodsThis Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27+5 and 33+5 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome. In participants allocated to receive immediate delivery, either induction of labor or cesarean section was initiated at least 48 hours after admission. Primary outcomes were adverse perinatal outcome, defined as a composite of severe respiratory distress syndrome, bronchopulmonary dysplasia, culture proven sepsis, intraventricular hemorrhage grade 3 or worse, periventricular leukomalacia grade 2 or worse, necrotizing enterocolitis stage 2 or worse, and perinatal death. Major maternal complications were secondary outcomes. It was estimated 1130 women needed to be enrolled. Analysis was by intention-to-treat.ResultsThe trial was halted after 35 months because of slow recruitment. Between February 2011 and December 2013, a total of 56 women were randomized to immediate delivery (n = 26) or temporizing management (n = 30). Median gestational age at randomization was 30 weeks. Median prolongation of pregnancy was 2 days (interquartile range 1-3 days) in the temporizing management group. Mean birthweight was 1435 g after immediate delivery vs 1294 g after temporizing management (P = .14). The adverse perinatal outcome rate was 55% in the immediate delivery group vs 52% in the temporizing management group (relative risk 1.06; 95% confidence interval 0.67-1.70). In both groups there was one neonatal death and no maternal deaths. In the temporizing treatment group, one woman experienced pulmonary edema and one placental abruption. Analyses of only the singleton pregnancies did not result in other outcomes.ConclusionsEarly termination of the trial precluded any conclusions for the main outcomes. We observed that temporizing management resulted in a modest prolongation of pregnancy without changes in perinatal and maternal outcome. Conducting a randomized study for this important research question did not prove feasible.

Project description:AIM/BACKGROUND:The prevalence of elderly pregnancy and maternal obesity is increasing worldwide. In old and obese women, metabolic derangement affecting fetal growth might be present earlier than the diagnosis of gestational diabetes mellitus (GDM) or even before pregnancy. We thus investigated whether GDM diagnosed at 24-28 weeks of gestation had already affected fetal abdominal growth and, if so, whether elderly pregnancy and/or maternal obesity aggravate fetal abdominal obesity. METHODS:We retrospectively reviewed the medical records of 7820 singleton pregnant women who had been universally screened using a 50-g glucose challenge test (GCT) at 24-28 weeks of gestation, and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT were ≥140mg/dl. GDM and normal glucose tolerance (NGT) were diagnosed using the Carpenter-Coustan criteria. Fetal abdominal obesity was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter or femur length, respectively. Fetal abdominal overgrowth was defined as FAOR ≥ 90th percentile. The subjects were divided into four study groups: group 1 (age < 35 years and pre-pregnancy body mass index [BMI] < 25 kg/m2), group 2 (age < 35 years and ≥ 25), group 3 (age ≥ 35 years and BMI < 25), and group 4 (age ≥ 35 years and ≥ 25). RESULTS:The overall prevalence of GDM was 5.1%, with old and obese group 4 exhibiting the highest prevalence (22.4%). FAORs were significantly higher in the fetus of those with GDM than in the NGT subjects. But, in the subgroup analysis, only old and nonobese group 3 and old and obese group 4 with GDM exhibited significantly higher FAORs than the NGT subjects. Also, risk of fetal abdominal overgrowth was increased in group 3 and 4 subjects with GDM but not in young and nonobese group 1 GDM. The risk of fetal abdominal overgrowth significantly increased with maternal age >35 years, pre-pregnancy BMI >20kg/m2, and HbA1c >37.7 mmol/mol (5.6%). In multivariate analyses, maternal age and HbA1c were significantly associated with FAORs. CONCLUSION:GDM diagnosed at 24-28 weeks of gestation already affected fetal abdominal obesity in older and/or obese women, but not in younger and nonobese women. Our data suggest that selective screening and appropriate intervention of GDM earlier than 24-28 weeks of gestation might be necessary for high-risk old and/or obese women.

Dataset Information

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

Similar Datasets

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