Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent

Abstract

Objective This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences.

Study Design The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent.

Results Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p < 0.001). At sites with an option of either approaching families before delivery or after delivery with a waiver of antenatal consent, those approached prior to delivery refused consent 40% (range 15–74% across six sites) of the time.

Conclusion PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects.

Clinical Trial Registration ClinicalTrials.gov identifier: NCT03019367.

Key Points

• Waiver of consent is when informed consent cannot be obtained prior to delivery.

• Cord milking is a procedure in which blood is pushed (stripped) two to four times towards the newborn.

• Delayed clamping means the umbilical cord is not clamped immediately after birth.

Keywords

cord milking - delayed cord clamping - waiver of consent

Authors' Contributions

A.C.K. conceptualized and designed the study, drafted the initial manuscript, designed the data collection instruments, coordinated and supervised data collection, and approved the final manuscript as submitted. J.E., J.K., E.D., G.M.S., M.V., F.V., W.C., T.Y., and S.B. performed the initial analyses, and coordinated and supervised data collection, reviewed and revised the manuscript, and approved the final manuscript as submitted. K.A., P.A., W.R., and J.M.S. collected the data, performed the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publikationsverlauf

Eingereicht: 15. September 2020

Angenommen: 06. Oktober 2020

Artikel online veröffentlicht:
03. November 2020

• References

• 1 Wiswell TE, Graziani LJ, Kornhauser MS. et al. Effects of hypocarbia on the development of cystic periventricular leukomalaécia in premature infants treated with high-frequency jet ventilation. Pediatrics 1996; 98 (05) 918-924
• 2 Kapadia VS, Chalak LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH. Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics 2013; 132 (06) e1488-e1496
• 3 Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 2015; 136 (01) 61-69
• 4 Katheria AC, Sauberan JB, Akotia D, Rich W, Durham J, Finer NN. A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 2015; 32 (09) 879-886
• 5 Katheria A, Reister F, Essers J. et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 2019; 322 (19) 1877-1886
• 6 Al-Wassia H, Shah PS. Efficacy and safety of umbilical cord milking at birth: a systematic review and meta-analysis. JAMA Pediatr 2015; 169 (01) 18-25
• 7 Finer NN, Carlo WA, Walsh MC. et al. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010; 362 (21) 1970-1979
• 8 Rich W, Finer NN, Gantz MG. et al. SUPPORT and Generic Database Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Enrollment of extremely low birth weight infants in a clinical research study may not be representative. Pediatrics 2012; 129 (03) 480-484
• 9 Katheria AC, Harbert MJ, Nagaraj SB. et al. The Neu-Prem trial: neuromonitoring of brains of infants born preterm during resuscitation-a prospective observational cohort study. J Pediatr 2018; 198: 209-213.e3
• 10 Songstad NT, Roberts CT, Manley BJ, Owen LS, Davis PG. HIPSTER trial investigators. Retrospective consent in a neonatal randomized controlled trial. Pediatrics 2018; 141 (01) e20172092
• 11 Rich WD, Katheria AC. Waiver of consent in a trial intervention occurring at birth-how do parents feel?. Front Pediatr 2017; 5: 56
• 12 Arnup SJ, Forbes AB, Kahan BC, Morgan KE, McDonald S, McKenzie JE. The use of the cluster randomized crossover design in clinical trials: protocol for a systematic review. Syst Rev 2014; 3: 86-86
• 13 Barbui C, Cipriani A. Cluster randomised trials. Epidemiol Psychiatr Sci 2011; 20 (04) 307-309