Dataset Information

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

ABSTRACT:

Introduction

There 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 methods

This 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.

Results

The 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.

Conclusions

Early 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.

SUBMITTER: Duvekot JJ

PROVIDER: S-EPMC7754130 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

Duvekot Johannes J JJ Duijnhoven Ruben G RG van Horen Eva E Bax Caroline J CJ Bloemenkamp Kitty W KW Brussé Ingrid A IA Dijk Peter H PH Franssen Maureen T MT Franx Arie A Oudijk Martijn A MA Porath Martina M MM Scheepers Hubertina C HC van Wassenaer-Leemhuis Aleid G AG van Drongelen Joris J Mol Ben W BW Ganzevoort Wessel W

Acta obstetricia et gynecologica Scandinavica 20200828 1

<h4>Introduction</h4>There 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.<h4>Material and methods</h4>This 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 ...[more]

PMID: 33319930

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Project description:ImportanceAspirin 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.ObjectiveTo 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 participantsMulticenter, 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.InterventionsEnrolled 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 measuresNoninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%.ResultsAmong 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 relevanceAspirin 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 registrationClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Project description:BackgroundWomen with bilateral abnormal uterine artery Doppler velocimetry (UtADV) are at increased risk for an adverse pregnancy outcome. This study aimed to determine if additional assessment of midtrimester angiogenic factors improves the predictive accuracy of Doppler results for various outcome parameters.MethodsWomen with a bilateral abnormal UtADV, which was defined as a postsystolic incision and/or an increased pulsatility index greater than the 95th centile, and a singleton pregnancy were prospectively recruited between 19 + 0 and 26 + 6 weeks of gestation. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured with a fully automated immunoassay and their ratio was calculated.ResultsAngiogenic factors could predict the development of preeclampsia (PE), as well as induced delivery at <34 weeks of gestation, but failed to predict the development of normotensive intrauterine growth restriction. Twelve (24.0%) of the 50 recruited women developed PE. Nine of these patients had early-onset disease (<34 + 0 weeks). Six (12.0%) patients were delivered at <34 + 0 weeks. The most useful test results in the prediction of PE and induced delivery at <34 + 0 weeks were observed using the sFLT-1/PlGF >95th centile ratio with a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 66.7%, 89.5%, 66.7%, and 89.5% for PE, and 85.7%, 86.1%, 50.1%, and 97.4% for induced delivery, respectively. Positive and negative likelihood ratios were 6.33 (95% CI 2.31-17.38) and 0.37 (95% CI 0.17-0.84) for PE, and 6.14 (95% CI 2.76-13.69) and 0.17 (0.03-1.02) for induced delivery, respectively. Corresponding odds ratios were 17.0 (95% CI 3.5-83.0) and 37.0 (95% CI 3.8-363.9), respectively.ConclusionsMeasurement of angiogenic factors improves the specificity of an abnormal UtADV for prediction of PE. Compared with prediction of PE an abnormal sFLT-1/PlGF ratio revealed higher sensitivity for prediction of induced delivery at <34 + 0 weeks. The NPV of 97% will help to reassure most patients with an abnormal UtADV and a normal sFLT-1/PlGF ratio.

Project description:BackgroundEvidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation.MethodsIn this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31-33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149.FindingsBetween March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: -1·6 (SD 1·2) in the 4 month group versus -1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI -0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0-3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group.InterpretationAlthough there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation.FundingIndian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Gupta's salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

Project description:Background Respiratory distress is common during transition after birth, but the effect of continuous positive airway pressure applied in the delivery room has not been systematically evaluated in spontaneously breathing term and ≥34+0 weeks’ gestation infants. We aimed to compare delivery room continuous positive airway pressure with no delivery room continuous positive airway pressure for term and ≥34+0 weeks’ gestation newborn infants at birth. Methods Information sources: Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and Cumulative Index to Nursing and Allied Health Literature. The Databases were last searched in October 2021. Eligibility criteria: Randomized, quasi-randomized, interrupted time series, controlled before-after, and cohort studies with English abstracts. Synthesis of results: Two authors independently extracted data, assessed risk of bias, and certainty of evidence. The main outcome was admission to the neonatal intensive care unit (NICU) or higher level of care receiving any positive pressure support. Data were pooled using fixed effects models. Risk of bias: Was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Non-Randomized Studies of Interventions Tool (ROBINS-I) for observational studies. Results In this meta-analysis, two randomized control trials (323 newborns delivered by cesarean section) showed that delivery room continuous positive airway pressure decreased the likelihood of NICU admission (risk ratio (RR) 95% confidence interval (CI) 0.27 (0.11–0.66), p < 0.005) and NICU respiratory support (RR (95% CI) 0.18 (0.05–0.60), p = 0.005) when compared with no delivery room continuous positive airway pressure. However, in two before-after studies (8,476 newborns), delivery room continuous positive airway pressure use was associated with an increased risk of air leak syndrome when compared with no delivery room continuous positive airway pressure. Discussion Certainty of evidence was very low for all outcomes. Among term and ≥34+0 weeks’ gestation infants having or at risk of having respiratory distress, there is insufficient evidence to suggest for or against routine use of continuous positive airway pressure in the delivery room. Funding: No Funding has been received to conduct this study. Clinical Trial Registration: This systematic review has been registered with the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/prospero/) [identifier: CRD42021225812].

Dataset Information

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

Introduction

Material and methods

Results

Conclusions

Publications

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

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