Feasibility Study of Early Blood Pressure Management in Extremely Preterm Infants

doi:10.1016/j.jpeds.2012.01.014

The Journal of Pediatrics

Volume 161, Issue 1, July 2012, Pages 65-69.e1

https://doi.org/10.1016/j.jpeds.2012.01.014 Get rights and content

Objective

To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants.

Study design

This was a prospective pilot RCT of infants 23-0/7 to 26-6/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo).

Results

Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. A total of 161 infants (44%) were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study because of the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin.

Conclusions

This pilot RCT was not feasible because of low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.

Section snippets

Methods

Inborn infants born 23-0/7 to 26-6/7 weeks GA at one of 7 collaborating Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers were eligible for this study when they had protocol-defined low BP. Exclusion criteria included a major birth defect, a decision to withhold or withdraw care, absence of an umbilical arterial catheter (UAC), or receipt of >20 mL/kg of fluid boluses, indomethacin, or ibuprofen before enrollment. Informed

Results

From Dec 3, 2009, to Dec 3, 2010, there were 366 inborn infants 23 to 26 weeks GA admitted to the neonatal intensive care unit of a participating NRN center (Figure). Fifty-eight infants (16%) were eligible for the study, and 10 infants (3%) were enrolled. There were 339 infants (93%) born to mothers who received at least one dose of a glucocorticoid before delivery, a UAC was placed in 307 infants (84%), and 119 infants (33%) had protocol-defined low BP. Because of low recruitment, midway

Discussion

In this pilot study to assess the feasibility of an RCT of BP management in extremely preterm infants, a low percentage of infants met all eligibility criteria, few eligible infants were enrolled, and a protocol deviation occurred in 20% of enrolled infants. The study did not achieve its primary objective. Several major factors hindered success, including fewer than anticipated infants with low BP, high rates of early indomethacin administration, difficulty obtaining informed consent, and a

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To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation).
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Citation Excerpt :
There is an unwillingness among clinicians to join a trial that addresses hemodynamic problems in neonatal intensive care, even though there is emerging physiologic and clinical evidence that alternative approaches are safe and possibly more effective. Two recent trials exploring the treatment of hypotension and the PDA could only enroll 17% and 24% of the eligible infants respectively.116,117 Barriers to enrollment included lack of physician equipoise leading to fewer parents being approached and infants in the trial given open label treatments.
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: The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development provided grant support, including funding from the Best Pharmaceuticals for Children Act, for the Neonatal Research Network’s Early Blood Pressure Pilot Study. Data collected at participating sites of the National Institute of Child Health and Human Development Neonatal Research Network were transmitted to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. The authors declare no conflicts of interest.

: Registered with ClinicalTrials.gov: NCT00874393.

^∗: A list of members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network is available at www.jpeds.com (Appendix).

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Original ArticleFeasibility Study of Early Blood Pressure Management in Extremely Preterm Infants

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Mean arterial pressures during the first 24 hours of life in ≤600-gram birth weight infants

J Perinatol

Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life

Early Hum Dev

Blood pressure standards for very low birthweight infants during the first day of life

Arch Dis Child

Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns

Arch Dis Child Fetal Neonatal Ed

Variations in prevalence of hypotension, hypertension and vasopressor use in NICUs

J Perinatol

Diagnostic criteria and therapeutic interventions for the hypotensive very low birth weight infant

J Perinatol

Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week

Pediatrics

Development of audit measures and guidelines for good practice in the management of neonatal respiratory distress syndrome

Arch Dis Child

Prospective evaluation of postnatal steroid administration: a 1-year experience from the California Perinatal Quality Care Collaborative

Pediatrics

The haemodynamic effects of dopamine and volume expansion in sick preterm infants

Early Hum Dev

A double-blind randomized, control study of a “stress dose” of hydrocortisone for rescue treatment of refractory hypotension in preterm infants

Pediatrics

Blood pressure during the first 7 days in premature infants born at postmenstrual age 23 to 25 weeks

Am J Perinatol

Permissive hypotension in the extremely low birth weight infant with signs of good perfusion

Arch Dis Child Fetal Neonatal Ed

Blood pressure, anti-hypotensive therapy, and neurodevelopment in extremely preterm infants

J Pediatr

Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns

J Perinatal

Original Article
Feasibility Study of Early Blood Pressure Management in Extremely Preterm Infants