Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for Gestational Age Fetuses – A Prospective Cohort Study

Abstract

Purpose To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements.

Methods Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3–10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol.

Results A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63).

Conclusion SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the “worst” CPR or mUtA PI but it remains moderate.

Zusammenfassung

Ziel Beschreibung des perinatalen Outcomes einer prospektiven Kohorte von „small for gestational age“ (SGA)-Feten sowie Vorhersage eines schlechten perinatalen Outcomes (APO) mittels longitudinaler Dopplermessungen.

Material und Methode Eingeschlossen wurden Einlingsschwangerschaften ab 32 + 0 Schwangerschaftswochen mit Verdacht auf SGA (Untersuchungen alle 2 Wochen) und gesunde Kontrollen. Die folgenden Dopplermessungen wurden ermittelt: Pulsatilitätsindex (PI) der Nabelschnurarterie (UA), PI der mittleren Zerebralarterie (MCA-PI), die zerebroplazentare Ratio (CPR) und mittlerer PI der Uterinarterien (mUtA-PI). APO wurde definiert als arterieller Nabelschnurblut-pH-Wert ≤ 7,15 und/oder 5-Minuten-Apgar ≤ 7 und/oder operative Notfall-Entbindung und/oder Aufnahme auf die Neugeborenenstation. Eine Geburtseinleitung bei SGA wurde nach Protokoll indiziert.

Ergebnisse Insgesamt wurden 149 SGA- und 143 Kontrollfeten eingeschlossen. Die Anzahl der operativen Entbindungen war in beiden Gruppen ähnlich, insbesondere die sekundäre Sectiorate (11 % vs. 10 %). Bei den meisten SGA-Fällen wurde die Geburt eingeleitet (61 % vs. 31 %; p < 0,001). Die Fläche unter der Kurve (AUC) für die APO-Vorhersage war unter Verwendung des letzten UA, MCA-PI, CPR und mUtA PI ähnlich und erreichte kaum 0,60; am besten war sie für die FGR-Subgruppe unter Verwendung der minimalen CPR oder des maximalen mUtA-PI (AUC = 0,63).

Schlussfolgerung SGA-Feten haben keine erhöhte operative Entbindungsrate, wenn sie nach einem Risikostratifizierungsprotokoll überwacht und entbunden werden. Die Vorhersage des APO ist am besten mit der „schlechtesten“ CPR oder mUtA-PI, aber sie ist insgesamt moderat.

Key words

late-onset small for gestational age - fetal growth restriction - feto-maternal Doppler - Doppler changes - SGA

Publication History

Received: 09 January 2021

Accepted: 19 April 2021

Article published online:
08 June 2021

• References

• 1 Savchev S, Figueras F, Cruz-Martinez R. et al. Estimated weight centile as a predictor of perinatal outcome in small-for-gestational-age pregnancies with normal fetal and maternal Doppler indices. Ultrasound Obstet Gynecol 2012; 39: 299-303
• 2 Cruz-Martinez 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: 618-626
• 3 Veglia M, Cavallaro A, Papageorghiou A. et al. Small-for-gestational-age babies after 37 weeks: impact study of risk-stratification protocol. Ultrasound Obstet Gynecol 2018; 52: 66-71
• 4 Figueras F, Caradeux J, Crispi F. et al. Diagnosis and surveillance of late-onset fetal growth restriction. Am J Obstet Gynecol 2018; 218: S790-S802.e1
• 5 Rial-Crestelo M, Martinez-Portilla RJ, Cancemi A. et al. Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies. J Matern Fetal Neonatal Med 2019; 32: 2554-2560
• 6 Sirico A, Diemert A, Glosemeyer P. et al. Prediction of adverse perinatal outcome by cerebroplacental ratio adjusted for estimated fetal weight. Ultrasound Obstet Gynecol 2018; 51: 381-386
• 7 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
• 8 Akolekar R, Ciobanu A, Zingler E. et al. Routine assessment of cerebroplacental ratio at 35–37 weeks' gestation in the prediction of adverse perinatal outcome. Am J Obstet Gynecol 2019; 221: 65.e1-65.e18
• 9 Khalil A, Morales-Rosello 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 Marsal K, Persson PH, Larsen T. et al. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 1996; 85: 843-848
• 11 Hadlock FP, Deter RL, Harrist RB. et al. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 1984; 152: 497-501
• 12 Voigt M, Rochow N, Schneider KT. et al. [New percentile values for the anthropometric dimensions of singleton neonates: analysis of perinatal survey data of 2007–2011 from all 16 states of Germany]. Zeitschrift fur Geburtshilfe und Neonatologie 2014; 218: 210-217
• 13 Arduini D, Rizzo G. Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 1990; 18: 165-172
• 14 Gomez O, Figueras F, Fernandez S. et al. Reference ranges for uterine artery mean pulsatility index at 11–41 weeks of gestation. Ultrasound Obstet Gynecol 2008; 32: 128-132
• 15 Baschat AA, Gembruch U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 2003; 21: 124-127
• 16 Schneider SL. The International Standard Classification of Education 2011. Comp Soc Res 2013; 30: 365-379
• 17 Figueras F, Gratacos E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther 2014; 36: 86-98
• 18 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-845
• 19 Robin X, Turck N, Hainard A. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011; 12: 77
• 20 Eixarch E, Meler E, Iraola A. et al. Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008; 32: 894-899
• 21 Nwabuobi C, Gowda N, Schmitz J. et al. Risk factors for Cesarean delivery in pregnancies with a small-for-gestational-age fetus undergoing induction of labor. Ultrasound Obstet Gynecol 2020; 55: 799-805
• 22 Buca D, Rizzo G, Gustapane S. et al Diagnostic Accuracy of Doppler Ultrasound in Predicting Perinatal Outcome in Appropriate for Gestational Age Fetuses: A Prospective Study. Ultraschall in Med 2020; [online ahead of print]
• 23 Ciardulli A, D'Antonio F, Caissutti C. et al Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome. J Matern-Fetal Neo M 2019; 1-7 [online ahead of print]
• 24 Khalil A, Morales-Rosello J, Khan N. et al. Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome?. American Journal of Obstetrics and Gynecology 2017; 216: 606.e1-606.e10
• 25 Conde-Agudelo A, Villar J, Kennedy SH. et al. Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis. Ultrasound Obst Gyn 2018; 52: 430
• 26 Hecher K, Bilardo CM, Stigter RH. et al. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. Ultrasound Obstet Gynecol 2001; 18: 564-570
• 27 Turan OM, Turan S, Gungor S. et al. Progression of Doppler abnormalities in intrauterine growth restriction. Ultrasound Obstet Gynecol 2008; 32: 160-167
• 28 Kalafat E, Ozturk E, Sivanathan J. et al. Longitudinal change in cerebroplacental ratio in small-for-gestational-age fetuses and risk of stillbirth. Ultrasound Obstet Gynecol 2019; 54: 492-499
• 29 Flatley C, Greer RM, Kumar S. Magnitude of change in fetal cerebroplacental ratio in third trimester and risk of adverse pregnancy outcome. Ultrasound Obstet Gynecol 2017; 50: 514-519
• 30 Oros D, Figueras F, Cruz-Martinez R. et al. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in late-onset small-for-gestational age fetuses. Ultrasound Obstet Gynecol 2011; 37: 191-195