Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome

Journal article


Akolekar, R., Ciobanu, A., Zingler, E., Syngelaki, A. and Nicolaides, K.H. 2019. Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. American Journal of Obstetrics & Gynecology. 221 (1), pp. 65.e1-65.e18. https://doi.org/10.1016/j.ajog.2019.03.002
AuthorsAkolekar, R., Ciobanu, A., Zingler, E., Syngelaki, A. and Nicolaides, K.H.
Abstract

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.

KeywordsThird trimester screening; Small for gestational age; Umbilical artery Doppler; Middle cerebral artery Doppler; Cerebroplacental ratio; Adverse perinatal outcome
Year2019
JournalAmerican Journal of Obstetrics & Gynecology
Journal citation221 (1), pp. 65.e1-65.e18
PublisherElsevier
ISSN0002-9378
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ajog.2019.03.002
Official URLhttp://doi.org/10.1016/j.ajog.2019.03.002
Related URLhttps://www.sciencedirect.com/science/article/pii/S0002937819304776
Publication dates
Online13 Mar 2019
Publication process dates
Accepted07 Mar 2019
Deposited15 Jun 2020
Accepted author manuscript
Output statusPublished
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Giacchino, Tara, Karkia, Rebecca, Zhang, Weiyu, Ahmed, Hasib and Akolekar, Ranjit 2021. Kielland’s rotational forceps delivery: comparison of maternal and neonatal outcomes with pregnancies delivering by non-rotational forceps. Journal of Obstetrics and Gynaecology. 42 (3), pp. 379-384. https://doi.org/10.1080/01443615.2021.1907557
Reference ranges for the pulsed wave doppler of the fetal cardiac inflow and outflow tracts from 13 to 36 weeks gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores.
Zidere, V., Vigneswaran, T. V., Syngelaki, A., Charakida, M., Allan, L. D., Nicolaides, K. H., Simpson, J. M and Akolekar, R. 2021. Reference ranges for the pulsed wave doppler of the fetal cardiac inflow and outflow tracts from 13 to 36 weeks gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. https://doi.org/S0894-7317(21)00467-3
Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities
Ficara, A., Syngelaki, A., Hammami, A., Akolekar, R. and Nicolaides, K. H. 2020. Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of fetal abnormalities. Ultrasound in Obstetrics and Gynecology. 55 (1), pp. 75-80. https://doi.org/10.1002/uog.20857
Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination
Syngelaki, A., Cimpoca, B., Litwinska, E., Akolekar, R. and Nicolaides, K. H. 2020. Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination. Ultrasound in Obstetrics and Gynecology. 55 (4), pp. 474-481. https://doi.org/10.1002/uog.21938
Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring
Panagiotopoulou, O., Syngelaki, A., Georgiopoulos, G., Simpson, J., Akolekar, R., Shehata, H., Nicolaides, K. H. and Charakida, M. 2020. Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2020.01.054
ISUOG Consensus Statement on organization of routine and specialist obstetric ultrasound services in the context of COVID-19
Abu-Rustum, R. S., Akolekar, R., Sotiriadis, A., Salomon, L. J., Da Silva Costa, F., Wu, Q., Frusca, T., Bilardo, C. M., Prefumo, F. and Poon, L. C. 2020. ISUOG Consensus Statement on organization of routine and specialist obstetric ultrasound services in the context of COVID-19. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.22029
Comparison of different methods of measuring angle of progression in prediction of labor outcome
Frick, A., Kostiv, V., Vojtassakova, D., Akolekar, R. and Nicolaides, K. H. 2020. Comparison of different methods of measuring angle of progression in prediction of labor outcome. Ultrasound in Obstetrics & Gynecology. 55 (3), pp. 391-400. https://doi.org/10.1002/uog.21913
Value of routine ultrasound examination at 35–37 weeks' gestation in diagnosis of non‐cephalic presentation
De Castro, H., Ciobanu, A., Formuso, C., Akolekar, R. and Nicolaides, K. H. 2020. Value of routine ultrasound examination at 35–37 weeks' gestation in diagnosis of non‐cephalic presentation. Ultrasound in Obstetrics & Gynecology. 55 (2), pp. 248-256. https://doi.org/10.1002/uog.21902
Impaired placental perfusion and major fetal cardiac defects
Fantasia, I., Andrade, W., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Impaired placental perfusion and major fetal cardiac defects. Ultrasound in Obstetrics and Gynecology. 53 (1), pp. 68-72. https://doi.org/10.1002/uog.20149
Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test
Galeva, S., Konstantinidou, L., Gil, M.M., Akolekar, R. and Nicolaides, K.H. 2019. Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test. Ultrasound in Obstetrics and Gynecology. 53 (2), pp. 208-213. https://doi.org/10.1002/uog.20160
ALEX Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index and cerebroplacental ratio
Ciobanu, A., Wright, A., Syngelaki, A., Wright, D., Akolekar, R. and Nicolaides, K.H. 2019. ALEX Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index and cerebroplacental ratio. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 465-472. https://doi.org/10.1002/uog.20157
Prediction of adverse perinatal outcome by cerebroplacental ratio in women undergoing induction of labor
Fiolna, M., Kostiv, V., Anthoulakis, C., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of adverse perinatal outcome by cerebroplacental ratio in women undergoing induction of labor. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 473-480. https://doi.org/10.1002/uog.20173
Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation
Ciobanu, A., Rouvali, A., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation. American Journal of Obstetrics & Gynecology. 220 (5), pp. 486.e1-486.e11. https://doi.org/10.1016/j.ajog.2019.01.227
Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks
Ciobanu, A., Formuso, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (4), pp. 488-495. https://doi.org/10.1002/uog.20243
Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates
Ciobanu, A., Khan, N., Syngelaki, A., Akolekar, R. and Nicolaides, K. H. 2019. Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates. Ultrasound in Obstetrics and Gynecology. 53 (6), pp. 761-768. https://doi.org/10.1002/uog.20258
Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks
Ciobanu, A., Anthoulakis, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (5), pp. 630-637. https://doi.org/10.1002/uog.20267
Maternal and neonatal complications of fetal macrosomia: cohort study
Beta, J., Khan, N., Fiolna, M., Khalil, A., Ramadan, G. and Akolekar, R. 2019. Maternal and neonatal complications of fetal macrosomia: cohort study. Ultrasound in Obstetrics and Gynecology. 54 (3), pp. 319-325. https://doi.org/10.1002/uog.20279
Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis
Beta, J., Zhang, W., Geris, S., Kostiv, V. and Akolekar, R. 2019. Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 452-457. https://doi.org/10.1002/uog.20293
Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Ciobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H. 2019. Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 54 (1), pp. 79-86. https://doi.org/10.1002/uog.20346
Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis
Salomon, L. J., Sotiriadis, A., Wulff, C. B., Odibo, A. and Akolekar, R. 2019. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 442-451. https://doi.org/10.1002/uog.20353
Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound
Khan, N., Ciobanu, A., Karampitsakos, T., Akolekar, R. and Nicolaides, K. H. 2019. Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound. Ultrasound in Obstetrics and Gynecology. 54 (2), pp. 326-333. https://doi.org/10.1002/uog.20377
Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation
Akolekar, R., Panaitescu, A. M., Ciobanu, A., Syngelaki, A. and Nicolaides, K. H. 2019. Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 54, pp. 484-491. https://doi.org/10.1002/uog.20391
Prevention of stillbirths: impact of a two-stage screening for vasa previa
Zhang, W., Geris, S., Beta, J., Ramadan, G., Nicolaides, K. H. and Akolekar, R. 2019. Prevention of stillbirths: impact of a two-stage screening for vasa previa. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 605-612. https://doi.org/10.1002/uog.21953
Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta
Vigneswaran, T. V., Zidere, V., Chivers, S., Charakida, M., Akolekar, R. and Simpson, J. M. 2019. Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.21957
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus
Minnella, G. P., Crupano, F. M., Syngelaki, A., Zidere, V., Akolekar, R. and Nicolaides, K. H. 2019. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 637-644. https://doi.org/10.1002/uog.21956
Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation
Dragan, I., Georgiou, T., Prodan, N., Akolekar, R. and Nicolaides, K. H. 2017. Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (1), pp. 73-77. https://doi.org/10.1002/uog.17301
Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (3), pp. 308-315. https://doi.org/10.1002/uog.14898
Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 194-202. https://doi.org/10.1002/uog.14928
Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result
Revello, R., Sarno, L., Ispas, A., Akolekar, R. and Nicolaides, K. H. 2016. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 698-704. https://doi.org/10.1002/uog.15851
Metformin versus placebo in obese pregnant women without diabetes mellitus
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., Pastides, A. and Shehata, H. 2016. Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine. 374, pp. 434-43. https://doi.org/10.1056/NEJMoa1509819
Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy
Sarno, L., Revello, R., Hanson, E., Akolekar, R. and Nicolaides, K. H. 2016. Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 705-11. https://doi.org/10.1002/uog.15913
Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks
Mastrodima, S., Akolekar, R., Yerlikaya, G., Tzelepis, T. and Nicolaides, K. H. 2016. Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 613-617. https://doi.org/10.1002/uog.17289
Prediction of stillbirth from maternal demographic and pregnancy characteristics
Yerlikaya, G., Akolekar, R., McPherson, K., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal demographic and pregnancy characteristics. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 607-612. https://doi.org/10.1002/uog.17290
Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies
Peeva, G., Chaveeva, P., Gil Guevara, E., Akolekar, R. and Nicolaides, K. H. 2016. Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies. Fetal Diagnosis and Therapy. 40 (3), pp. 174-180. https://doi.org/10.1159/000443792
Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks
Akolekar, R., Tokunaka, M., Ortega, N., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 624-630. https://doi.org/10.1002/uog.17295
Prediction of stillbirth from placental growth factor at 11-13 weeks
Akolekar, R., Machuca, M., Mendes, M., Paschos, V. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 618-623. https://doi.org/10.1002/uog.17288
Prediction of stillbirth from placental growth factor at 19-24 weeks
Aupont J. E., Akolekar, R., Illian, A., Neonakis, S. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 631-635. https://doi.org/10.1002/uog.17229
Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2015. Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 203-209. https://doi.org/10.1002/uog.15663