Background: Third trimester studies in selected high-risk pregnancies have reported that low cerebroplacental ratio (CPR), due to high pulsatility index (PI) in the umbilical artery (UA), and or decreased PI in the fetal middle cerebral artery (MCA), is associated with increased risk of adverse perinatal outcomes.
Objective: To investigate the predictive performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured routinely at 35+6 - 36+6 weeks’ gestation.
Methods: This was a prospective observational study in 47,211 women with singleton pregnancies undergoing routine ultrasound examination at 35+6 - 36+6 weeks’ gestation, including measurement of UA-PI and MCA-PI. The measured UA-PI and MCA-PI and their ratio were converted to multiples of the median (MoM) after adjustment for gestational age. Multivariable logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history and obstetric factors. The following outcome measures were considered: first, adverse perinatal outcome consisting of stillbirth, neonatal death or hypoxic ischemic encephalopathy grades 2 and 3, second, presence of surrogate markers of perinatal hypoxia consisting of umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score <7, or admission to the neonatal intensive care unit for >24 hours, third, cesarean section for presumed fetal distress in labor, and fourth, neonatal birthweight <3rd percentile for gestational age.
Results: Low CPR was associated with increased risk of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, cesarean section for presumed fetal distress in labor and birth of neonates with birthweight <3rd percentile. However, multivariable regression analysis demonstrated that the prediction of these adverse outcomes by maternal demographic characteristics and medical history was only marginally improved by the addition of CPR. The performance of low CPR in the prediction of each adverse outcome was poor, with detection rates of 13–26% and false positive rate of about 10%. In appropriate for gestational age (AGA) neonates with birthweight ≥10th percentile the predictive accuracy of CPR was low with positive and negative likelihood ratios (LRs) ranging from 1.21 to 1.82, and 0.92 to 0.98, respectively; although the accuracy was better in small for gestational age (SGA) neonates this was also low with positive LRs of 1.31 to 2.26 and negative LRs of 0.69 to 0.92. Similar values were obtained in fetuses classified as SGA and AGA according to the estimated fetal weight. In the prediction of adverse outcomes within two weeks, rather than at any stage, after assessment the detection rate was higher but this was achieved at higher false positive rate and therefore similar positive and negative LRs.
Conclusion: In pregnancies undergoing routine antenatal assessment at 35+0 - 36+6 weeks’ gestation measurement of CPR provides poor prediction of adverse perinatal outcome in both SGA and AGA fetuses. Consequently, there is no justification in a shift of the focus of prenatal care from identification of pregnancies with low estimated fetal weight to that of pregnancies with low CPR.
1.Nicolaides KH, Soothill PW, Rodeck CH,Campbell S. Ultrasound guided sampling ofumbilical cord and placental blood to assessfetal wellbeing. Lancet 1986;1:1065–7.
2.Soothill PW, Nicolaides KH, Campbell S.Prenatal asphyxia, hyperlacticaemia, hypo-glycaemia and erythroblastosis in growthretarded fetuses. BMJ 1987;294:1051–3.
3.Nicolaides KH, Bilardo KM, Soothill PW,Campbell S. Absence of end diastolicOriginal ResearchOBSTETRICSajog.org65.e10American Journal of Obstetrics&GynecologyJULY 2019
frequencies in the umbilical artery a sign offetal hypoxia and acidosis. BMJ 1988;297:1026–7.
4.Vyas S, Nicolaides KH, Bower S, Campbell S.Middle cerebral arteryflow velocity waveforms infetal hypoxaemia. Br J Obstet Gynaecol1990;97:797–803.
5.Bahado-Singh RO, Kovanci E, Jeffres A, et al.The Doppler cerebroplacental ratio and perinataloutcome in intrauterine growth restriction. Am JObstet Gynecol 1999;180:750–6.
6.Gramellini D, Folli MC, Raboni S, Vadora E,Merialdi A. Cerebral-umbilical Doppler ratio as apredictor of adverse perinatal outcome. ObstetGynecol 1992;79:416–20.
7.DeVore GR. The importance of the cere-broplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J ObstetGynecol 2015;213:5–15.
8.Flood K, Unterscheider J, Daly S, et al. Therole of brain sparing in the prediction of adverseoutcomes in intrauterine growth restriction: re-sults of the multicenter PORTO Study. Am JObstet Gynecol 2014;211:288.e1–5.
9.Prior T, Mullins E, Bennett P, Kumar S. Pre-diction of intrapartum fetal compromise usingthe cerebroumbilical ratio: a prospective obser-vational study. Am J Obstet Gynecol 2013;208:124.e1–6.
10.Khalil AA, Morales-Rosello J, Morlando M,et al. Is fetal cerebroplacental ratio an indepen-dent predictor of intrapartum fetal compromiseand neonatal unit admission? Am J ObstetGynecol 2015;213:54.e1–10.
11.Khalil AA, Morales-Rosello J, Elsadigg M,et al. The association between fetal Doppler andadmission to neonatal unit at term. Am J ObstetGynecol 2015;213:57.e1–7.
12.Khalil A, Morales-Rosello J, Khan N, et al. Iscerebroplacental ratio a marker of impaired fetalgrowth velocity and adverse pregnancyoutcome? Am J Obstet Gynecol 2017;216:606.e1–10.
13.Bakalis S, Akolekar R, Gallo DM, Poon LC,Nicolaides KH. Umbilical and fetal middlecerebral artery Doppler at 30-34 weeks’gestation in the prediction of adverse perinataloutcome. Ultrasound Obstet Gynecol2015;45:409–20.
14.Akolekar R, Syngelaki A, Gallo DM,Poon LC, Nicolaides KH. Umbilical and fetalmiddle cerebral artery Doppler at 35-37 weeks’gestation in the prediction of adverse perinataloutcome. Ultrasound Obstet Gynecol 2015;46:82–92.
15.Hammami A, Mazer Zumaeta A,Syngelaki A, Akolekar R, Nicolaides KH. Ultra-sonographic estimation of fetal weight: devel-opment of new model and assessment ofperformance of previous models. UltrasoundObstet Gynecol 2018;52:35–43.
16.Nicolaides KH, Wright D, Syngelaki A,Wright A, Akolekar R. Fetal Medicine Foundationfetal and neonatal population weight charts.Ultrasound Obstet Gynecol 2018;52:44–51.
17.Ciobanu A, Wright A, Syngelaki A, Wright D,Akolekar R, Nicolaides KH. Fetal MedicineFoundation reference ranges for umbilical arteryand middle cerebral artery pulsatility index andcerebroplacental ratio. Ultrasound ObstetGynecol 2019;53:465–72.
18.Robinson HP, Fleming JE. A critical evalua-tion of sonar crown rump length measurements.Br J Obstet Gynaecol 1975;82:702–10.
19.Snijders RJ, Nicolaides KH. Fetal biometry at14-40 weeks’gestation. Ultrasound ObstetGynecol 1994;4:34–48.
20.Yeh P, Emary K, Impey L. The relationshipbetween umbilical cord arterial pH and seriousadverse neonatal outcome: analysis of 51,519consecutive validated samples. BJOG2012;119:824–31.
21.Amer-Wahlin I, Arulkumaran S, Hagberg H,Marsál K, Visser GH. Fetal electrocardiogram:ST waveform analysis in intrapartum surveil-lance. BJOG 2007;114:1191–3.
22.National Collaborating Centre for Women’sand Children’s Health (UK). Intrapartum Care:Care of Healthy Women and Their Babies DuringChildbirth. National Institute for Health and CareExcellence: Clinical Guidelines; 2014.
23.Zweig MH, Campbell G. Receiver-operatingcharacteristic (ROC) plots: a fundamental eval-uation tool in clinical medicine. Clin Chem1993;39:561–77.
24.Vollgraff Heidweiller-Schreurs CA, DeBoer MA, Heymans MW, et al. Prognosticaccuracy of cerebroplacental ratio and middlecerebral artery Doppler for adverse perinataloutcome: systematic review and meta-analysis.Ultrasound Obstet Gynecol 2018;51:313–22.
25.Ciobanu A, Rouvali A, Syngelaki A,Akolekar R, Nicolaides KH. Prediction of smallfor gestational age neonates: Screening bymaternal factors and biomarkers at 35-37weeks’gestation. Am J Obstet Gynecol2019;220:486.e1–11.
26.Mendez-Figueroa H, Truong VT, Pedroza C,Khan AM, Chauhan SP. Small-for-gestational-age infants among uncomplicated pregnanciesat term: a secondary analysis of 9 Maternal-FetalMedicine Units Network studies. Am J ObstetGynecol 2016;215:628.e1–7.
27.Madden JV, Flatley CJ, Kumar S. Termsmall-for-gestational-age infants from low-riskwomen are at significantly greater risk ofadverse neonatal outcomes. Am J ObstetGynecol 2018;218:525.e1–9.
28.Bais JMJ, Eskes M, Pel M, Bonsel GJ,Bleker OP. Effectiveness of detection of intra-uterine retardation by abdominal palpation asscreening test in a low-risk population: anobservational study. Eur J Obstet GynecolReprod Biol 2004;116:164–9.
29.Lindhard A, Nielsen PV, Mouritsen LA,Zachariassen A, Sørensen HU, Rosenø H. Theimplications of introducing the symphyseal-fundal height-measurement. A prospective ran-domized controlled trial. Br J Obstet Gynaecol1990;97:675–80.
30.McCowan LM, Figueras F, Anderson NH.Evidence-based national guidelines for themanagement of suspected fetal growthrestriction: comparison, consensus, and con-troversy. Am J Obstet Gynecol 2018;218:S855–68.
31.David C, Tagliavini G, Pilu G, Rudenholz A,Bovicelli L. Receiver-operator characteristiccurves for the ultrasonographic prediction ofsmall-for-gestational-age fetuses in low-riskpregnancies. Am J Obstet Gynecol 1996;174:1037–42.
32.Bakalis S, Silva M, Akolekar R, Poon LC,Nicolaides KH. Prediction of small for gestationalage neonates: screening by fetal biometry at30e34 weeks. Ultrasound Obstet Gynecol2015;45:551–8.
33.Sovio U, White IR, Dacey A, Pasupathy D,Smith GCS. Screening for fetal growth re-striction with universal third trimester ultraso-nography in nulliparous women in thePregnancy Outcome Prediction (POP) study:a prospective cohort study. Lancet 2015;386:2089–97.
34.Gaccioli F, Aye ILMH, Sovio U, Charnock-Jones DS, Smith GCS. Screening for fetalgrowth restriction using fetal biometry combinedwith maternal biomarkers. Am J Obstet Gynecol2018;218:S725–37.
35.Figueras F, Caradeux J, Crispi F, Eixarch E,Peguero A, Gratacos E. Diagnosis and surveil-lance of late-onset fetal growth restriction. Am JObstet Gynecol 2018;218:S790–802.
36.CiobanuA, Khan N, Syngelaki A, Akolekar R,Nicolaides KH. Routine ultrasound at 30-34 and35-36 weeks’gestation: prediction of small forgestational age neonates. Ultrasound ObstetGynecol 2019 [In press].