Perinatal death in a term fetal growth restriction randomized controlled trial: the paradox of prior risk and consent

Linda Van Wyk,Kim E Boers,Sanne J Gordijn,Wessel Ganzevoort,Henk A Bremer,Anneke Kwee,Friso M.C Delemarre,Maria G Van Pampus,Kitty W.M Bloemenkamp,Frans J.M.E Roumen,Jan M.M Van Lith,Ben W.J Mol,Jim G Thornton,Sicco A Scherjon,Saskia Le Cessie

doi:10.1016/j.ajogmf.2020.100239

Abstract

The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes. To evaluate trial participation bias and to examine the generalizability of the results of an obstetrical randomized trial. We used data from participants and nonparticipants of a randomized controlled trial-the disproportionate intrauterine growth intervention trial at term (n=1116) -to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Data were collected in the same manner for both groups. Baseline characteristics and neonatal and maternal outcomes were compared. The primary outcome was a composite measure of adverse neonatal outcome. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity. Nonparticipants were older, had a lower body mass index, had a higher level of education, smoked less, and preferred expectant management. The time between study inclusion and labor onset was shorter in participants than in nonparticipants. Notably, 4 perinatal deaths occurred among nonparticipants and none among participants. Among nonparticipants, there were more children born with a birthweight below the third centile. The nonparticipants who had expectant management were monitored less frequently than the participants in both the intervention and the expectant arm. We found less favorable outcomes and more perinatal deaths in nonparticipants. Protocol-driven management, differences between participants and nonparticipants, or the fact that nonparticipants had a preference for expectant management might explain the findings.

Highlights

The factors that influence patient participation in trials are widely discussed.1e4 Patients’ choices to participate are, for example, influenced by individual preferences and socioeconomic background.[1,5] Participation in a clinical trial can lead to the so-called “Hawthorne effect.”[6]The original Hawthorne effect was first described between 1924 and 1933 where productivity of factory workers was increased while they—as part of a study to improve quality of the production process—were more strictly supervised.[7,8] It is unknown what the exactCite this article as: van Wyk L, Boers KE, Gordijn SJ, et al Perinatal death in a term fetal growth restriction randomized controlled trial: the paradox of prior risk and consent
Some studies report better outcome than expected, which is explained by the Hawthorne effect.9e11 Other studies report no such thing as the Hawthorne effect.12e14 A factor that could influence a possible Hawthorne effect is that characteristics of people who consent to participate in clinical trials often differ from patients who decline participation
Women who are less educated and with a lower socioeconomic status are often less willing to participate in clinical trials.15e19 in our study, we find the opposite; that is, highly educated women were less willing to be randomized for the trial

Summary

Introduction

The factors that influence patient participation in trials are widely discussed.1e4 Patients’ choices to participate are, for example, influenced by individual preferences and socioeconomic background.[1,5] Participation in a clinical trial can lead to the so-called “Hawthorne effect.”[6]The original Hawthorne effect was first described between 1924 and 1933 where productivity of factory workers was increased while they—as part of a study to improve quality of the production process—were more strictly supervised.[7,8] It is unknown what the exact. Some studies report better outcome (in both arms of a study) than expected, which is explained by the Hawthorne effect.9e11 Other studies report no such thing as the Hawthorne effect.12e14 A factor that could influence a possible Hawthorne effect is that characteristics of people who consent to participate in clinical trials often differ from patients who decline participation. The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes. STUDY DESIGN: We used data from participants and nonparticipants of a randomized controlled trial—the disproportionate intrauterine growth intervention trial at term (n1⁄41116) —to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity

Objectives

Methods

Results

Conclusion