Dataset Information

Association of Intraventricular Hemorrhage and Death With Tocolytic Exposure in Preterm Infants.

ABSTRACT:

Importance

No trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier.

Objectives

To assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocolysis with death and/or IVH.

Design, settings, and participants

The French 2011 EPIPAGE-2 (Enquête Épidémiologique sur les Petits Âges Gestationnels) cohort was limited to mothers admitted for preterm labor without fever, who delivered from 24 to 31 weeks of gestation from April 1 through December 31, 2011. Groups of preterm infants with vs without tocolytic exposure and groups with atosiban vs CCB exposure were compared. Data analysis was performed from June 7, 2014, through September 3, 2017.

Exposures

Tocolytics.

Main outcomes and measures

The primary outcome was a composite of death and/or IVH in preterm infants. Secondary outcomes included death, IVH, and a composite of death and/or grades III to IV IVH.

Results

A total of 1127 mothers (mean [SD] age, 25.5 [6.0] years) experienced preterm labor and gave birth to 1343 preterm infants with a male to female ratio of 1.23 and mean (SD) gestational age of 27?(2.5) weeks. Of these, 789 mothers (70.0%) received tocolytics; 314 (39.8%) received only atosiban, and 118 (15.0%) received only a CCB. In the first analysis, the primary outcome (death and/or IVH) was not significantly different in preterm infants with vs without tocolytic exposure (183 of 363 [50.4%] vs 207 of 363 [57.0%]; relative risk [RR], 0.88; 95% CI, 0.77-1.01; P?=?.07). The secondary outcome (death and/or grades III-IV IVH) was significantly lower in preterm infants with vs without tocolytic exposure (92 of 363 [25.3%] vs 118 of 363 [32.5%]; RR, 0.78; 95% CI, 0.62-0.98; P?=?.03). Other outcomes did not differ significantly. In the secondary analysis, death and/or IVH was not significantly different in preterm infants with atosiban vs CCB exposure (96 of 214 [44.9%] vs 62 of 121 [51.2%]; RR, 0.88; 95% CI, 0.70-1.10; P?=?.26), nor was IVH (77 of 197 [39.1%] vs 48 of 106 [45.3%]; RR, 0.86; 95% CI, 0.66-1.13; P?=?.29).

Conclusions and relevance

In this population-based study, findings suggest that tocolytics were associated with a reduction of death and severe IVH. Other studies are necessary to compare perinatal outcomes after use of atosiban vs CCBs.

SUBMITTER: Pinto Cardoso G

PROVIDER: S-EPMC6324618 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Association of Intraventricular Hemorrhage and Death With Tocolytic Exposure in Preterm Infants.

Pinto Cardoso Gaëlle G Houivet Estelle E Marchand-Martin Laetitia L Kayem Gilles G Sentilhes Loïc L Ancel Pierre-Yves PY Lorthe Elsa E Marret Stéphane S

JAMA network open 20180907 5

<h4>Importance</h4>No trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier.<h4>Objectives</h4>To assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocoly ...[more]

PMID: 30646165

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Project description:ImportanceUmbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation.ObjectiveTo determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping.Design, setting, and participantsNoninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018.InterventionsParticipants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238).Main outcomes and measuresThe primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin.ResultsAmong 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, -2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002).Conclusions and relevanceIn this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions.Trial registrationClinicalTrials.gov Identifier: NCT03019367.

Project description:Although chorioamnionitis (CA) is a well-known risk factor for white matter disease of prematurity, the association with intraventricular hemorrhage (IVH) is controversial and has not been yet systematically reviewed. We performed a systematic review and meta-analysis of studies exploring the association between CA and IVH. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 July 2017. Studies were included if they examined preterm infants and reported primary data that could be used to measure the association between exposure to CA and the presence of IVH. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). We found 1,284 potentially relevant studies, of which 85 met the inclusion criteria (46,244 infants, 13,432 CA cases). Meta-analysis showed that CA exposure was significantly associated with all grades IVH (OR 1.88, 95% CI 1.61-2.19), with grades 1-2 IVH (OR 1.69, 95% CI 1.22-2.34), and with grades 3-4 IVH (OR 1.62, 95% CI 1.42-1.85). Both clinical and histological CA were associated with an increased risk for developing IVH in very preterm infants. In contrast, the presence of funisitis did not increase IVH risk when compared to CA in the absence of funisitis (OR 1.22, 95% CI 0.89-1.67). Further meta-analyses confirmed earlier findings that CA-exposed infants have significantly lower gestational age (GA; mean difference [MD] -1.20 weeks) and lower birth weight (BW; MD -55 g) than the infants not exposed to CA. However, meta-regression and subgroup analysis could not demonstrate an association between the lower GA and BW and the risk of IVH in the CA-exposed infants. In conclusion, our data show that CA is a risk factor for IVH, but also a risk factor for greater prematurity and more clinical instability. In contrast to other complications of prematurity, such as patent ductus arteriosus, retinopathy of prematurity, or bronchopulmonary dysplasia, the effect of CA on IVH appears to be independent of CA as causative factor for very preterm birth.

Dataset Information

Association of Intraventricular Hemorrhage and Death With Tocolytic Exposure in Preterm Infants.

Importance

Objectives

Design, settings, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Intraventricular Hemorrhage and Death With Tocolytic Exposure in Preterm Infants.

Similar Datasets

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