Predicting intrapartum fetal compromise at term using the cerebroplacental ratio and placental growth factor levels (PROMISE) study: randomised controlled trial protocol

Helen Sherrell, Vicky Clifton, Sailesh Kumar, Helen Sherrell, Vicky Clifton, Sailesh Kumar

Abstract

Introduction: Intrapartum complications are a major contributor to adverse perinatal outcomes, including stillbirth, hypoxic-ischaemic brain injury and subsequent longer term disability. In many cases, hypoxia develops as a gradual process due to the inability of the fetus to tolerate the stress of parturition suggesting reduced fetoplacental reserve before labour commences. The fetal cerebroplacental ratio (CPR) is an independent predictor of intrapartum fetal compromise, poor acid base status at birth and of neonatal unit admission at term. Similarly, circulating maternal levels of placental growth factor (PlGF) are lower in pregnancies complicated by placental dysfunction. This paper outlines the protocol for the PROMISE Study, which aims to determine if the introduction of a prelabour screening test for intrapartum fetal compromise combining the CPR and maternal PlGF level results in a reduction of adverse perinatal outcomes.

Methods and analysis: This is a single-site, non-blinded, individual patient randomised controlled trial of a screening test performed at term, combining the fetal CPR and maternal serum PlGF. Women with a singleton, non-anomalous pregnancy will be recruited after 34 weeks' gestation and randomised to either receive the screening test or not. Screened pregnancies determined to be at risk will be recommended induction of labour. Demographic, obstetric history and antenatal data will be collected at enrolment, and perinatal outcomes will be recorded after delivery. Relative risks and 95% CIs will be reported for the primary outcome. Regression techniques will be used to examine the influence of prognostic factors on the primary and secondary outcomes.

Ethics and dissemination: This study has been reviewed and approved by the Mater Human Research Ethics Committee (Reference: HREC EC00332) and will follow the principles of Good Clinical Practice. The study results will be disseminated at national and international conferences and published in peer-reviewed journals.

Trial registration number: ACTRN12616001009404; Pre-results.

Keywords: cerebroplacental ratio; intrapartum fetal compromise; perinatal outcome; placental growth factor; screening test.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of study intervention and participant management. CPR, cerebroplacental ratio; PlGF, placental growth factor.

References

    1. Blencowe H, Cousens S, Jassir FB, et al. . National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health 2016;4:e98–e108. 10.1016/S2214-109X(15)00275-2
    1. Hilder L, Zhichao Z, Parker M, et al. . Australia’s Mothers and Babies 2012. Perinatal statistics series no. 30. Cat. no. PER 69. Canberra: AIHW 2014.
    1. Grace L, Greer RM, Kumar S. Perinatal consequences of a category 1 caesarean section at term. BMJ Open 2015;5:e007248 10.1136/bmjopen-2014-007248
    1. Mendez-Figueroa H, Truong VT, Pedroza C, et al. . Small-for-gestational-age infants among uncomplicated pregnancies at term: a secondary analysis of 9 Maternal-Fetal Medicine Units Network studies. Am J Obstet Gynecol 2016;215:628–e1-7. 10.1016/j.ajog.2016.06.043
    1. Bardien N, Whitehead CL, Tong S, et al. . Placental Insufficiency in Fetuses That Slow in Growth but Are Born Appropriate for Gestational Age: A Prospective Longitudinal Study. PLoS One 2016;11:e0142788 10.1371/journal.pone.0142788
    1. McIntyre S, Taitz D, Keogh J, et al. . A systematic review of risk factors for cerebral palsy in children born at term in developed countries. Dev Med Child Neurol 2013;55:499–508. 10.1111/dmcn.12017
    1. Low JA, Pickersgill H, Killen H, et al. . The prediction and prevention of intrapartum fetal asphyxia in term pregnancies. Am J Obstet Gynecol 2001;184:724–30. 10.1067/mob.2001.111720
    1. Fleischer A, Anyaegbunam AA, Schulman H, et al. . Uterine and umbilical artery velocimetry during normal labor. Am J Obstet Gynecol 1987;157:40–3. 10.1016/S0002-9378(87)80342-3
    1. Ebbing C, Rasmussen S, Kiserud T. Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: longitudinal reference ranges and terms for serial measurements. Ultrasound Obstet Gynecol 2007;30:287–96. 10.1002/uog.4088
    1. Severi FM, Bocchi C, Visentin A, et al. . Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002;19:225–8. 10.1046/j.1469-0705.2002.00652.x
    1. Cruz-Martínez R, Figueras F, Hernandez-Andrade E, et al. . Fetal brain Doppler to predict cesarean delivery for nonreassuring fetal status in term small-for-gestational-age fetuses. Obstet Gynecol 2011;117:618–26. 10.1097/AOG.0b013e31820b0884
    1. Cruz-Martinez R, Figueras F, Oros D, et al. . Cerebral blood perfusion and neurobehavioral performance in full-term small-for-gestational-age fetuses. Am J Obstet Gynecol 2009;201:474.e1–7. 10.1016/j.ajog.2009.05.028
    1. Prior T, Mullins E, Bennett P, et al. . Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective observational study. Am J Obstet Gynecol 2013;208:124.e1–6. 10.1016/j.ajog.2012.11.016
    1. Prior T, Mullins E, Bennett P, et al. . Prediction of fetal compromise in labor. Obstet Gynecol 2014;123:1263–71. 10.1097/AOG.0000000000000292
    1. Dunn L, Sherrell H, Kumar S. Review: Systematic review of the utility of the fetal cerebroplacental ratio measured at term for the prediction of adverse perinatal outcome. Placenta 2017;54:68–75. 10.1016/j.placenta.2017.02.006
    1. Khalil AA, Morales-Rosello J, Morlando M, et al. . Is fetal cerebroplacental ratio an independent predictor of intrapartum fetal compromise and neonatal unit admission? Am J Obstet Gynecol 2015;213:54.e1–10. 10.1016/j.ajog.2014.10.024
    1. Morales-Roselló J, Khalil A, Morlando M, et al. . Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio. Ultrasound Obstet Gynecol 2015;45:156–61. 10.1002/uog.14647
    1. DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 2015;213:5–15. 10.1016/j.ajog.2015.05.024
    1. Prior T, Paramasivam G, Bennett P, et al. . Are fetuses that fail to achieve their growth potential at increased risk of intrapartum compromise? Ultrasound Obstet Gynecol 2015;46:460–4. 10.1002/uog.14758
    1. Morales-Roselló J, Khalil A, Morlando M, et al. . Changes in fetal Doppler indices as a marker of failure to reach growth potential at term. Ultrasound Obstet Gynecol 2014;43:303–10. 10.1002/uog.13319
    1. Khalil A, Morales-Roselló J, Townsend R, et al. . Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss. Ultrasound Obstet Gynecol 2016;47:74–80. 10.1002/uog.15729
    1. Figueras F, Gratacos E, Rial M, et al. . Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol. BMJ Open 2017;7:e014835 10.1136/bmjopen-2016-014835
    1. Benton SJ, McCowan LM, Heazell AE, et al. . Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction. Placenta 2016;42:1–8. 10.1016/j.placenta.2016.03.010
    1. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, et al. . Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta-analysis. BJOG 2013;120:681–94. 10.1111/1471-0528.12172
    1. Torry DS, Mukherjea D, Arroyo J, et al. . Expression and function of placenta growth factor: implications for abnormal placentation. J Soc Gynecol Investig 2003;10:178–88. 10.1016/S1071-55760300048-0
    1. Osol G, Celia G, Gokina N, et al. . Placental growth factor is a potent vasodilator of rat and human resistance arteries. Am J Physiol Heart Circ Physiol 2008;294:H1381–7. 10.1152/ajpheart.00922.2007
    1. Vrachnis N, Kalampokas E, Sifakis S, et al. . Placental growth factor (PlGF): a key to optimizing fetal growth. J Matern Fetal Neonatal Med 2013;26:995–1002. 10.3109/14767058.2013.766694
    1. Herraiz AI, Dröge AL, Gómez-Montes AE, et al. . Characterization of the soluble fms-Like tyrosine kinase-1 to placental growth factor ratio in pregnancies complicated by fetal growth restriction. Obstet Gynecol 2014;124:265–73. 10.1097/AOG.0000000000000367
    1. Chappell LC, Duckworth S, Seed PT, et al. . Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation 2013;128:2121–31. 10.1161/CIRCULATIONAHA.113.003215
    1. Triunfo S, Lobmaier S, Parra-Saavedra M, et al. . Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion. Placenta 2014;35:398–403. 10.1016/j.placenta.2014.03.021
    1. Lobmaier SM, Figueras F, Mercade I, et al. . Angiogenic factors vs Doppler surveillance in the prediction of adverse outcome among late-pregnancy small-for- gestational-age fetuses. Ultrasound Obstet Gynecol 2014;43:533–40. 10.1002/uog.13246
    1. Bligh LN, Greer RM, Kumar S. The relationship between maternal placental growth factor levels and intrapartum fetal compromise. Placenta 2016;48:63–7. 10.1016/j.placenta.2016.10.007
    1. Bligh LN, Greer RM, Kumar S. Screening performance of placental growth factor for the prediction of low birth weight and adverse intrapartum and neonatal outcomes in a term low-risk population. Fetal Diagn Ther 2017. 10.1159/000480381
    1. Bligh LN, Alsolai AA, Greer RM, et al. . Pre-labour screening for intrapartum fetal compromise in low risk pregnancies at term: cerebroplacental ratio and placental growth factor. Ultrasound Obstet Gynecol 2017. 10.1002/uog.18981
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. . SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586 10.1136/bmj.e7586

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe