Effects of Antenatal Betamethasone on Fetal Doppler Indices and Short Term Fetal Heart Rate Variation in Early Growth Restricted Fetuses

Nicola Fratelli; Federico Prefumo; Hans Wolf; Kurt Hecher; Gerard H. A. Visser; Dino Giussani; Jan B. Derks; Caroline J. Shaw; Tiziana Frusca; Tullio Ghi; E. Ferrazzi; Christoph C. Lees; on behalf of the TRUFFLE Group; TRUFFLE Group authors; TRUFFLE Group collaborating authors

doi:10.1055/a-0972-1098

Ultraschall in der Medizin - European Journal of Ultrasound, Table of Contents

Ultraschall Med 2021; 42(01): 56-64
DOI: 10.1055/a-0972-1098

Original Article

Effects of Antenatal Betamethasone on Fetal Doppler Indices and Short Term Fetal Heart Rate Variation in Early Growth Restricted Fetuses

Einfluss von antenatalem Betamethason auf fetale Doppler-Indizes und die Kurzzeitvariation der fetalen Herzfrequenz bei Föten mit früher Wachstumsrestriktion

Nicola Fratelli

¹Department of Obstetrics and Gynaecology, University of Brescia, Spedali Civili di Brescia, Brescia, Italy

,

Federico Prefumo

¹Department of Obstetrics and Gynaecology, University of Brescia, Spedali Civili di Brescia, Brescia, Italy

,

Hans Wolf

²Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands

,

Kurt Hecher

³Department of Obstetrics and Fetal Medicine, University Medical Center, Hamburg-Eppendorf, Germany

,

Gerard H. A. Visser

⁴Department of Perinatal Medicine, University of Utrecht, Netherlands

,

Dino Giussani

⁵Department of Physiology Development & Neuroscience, University of Cambridge, United Kingdom of Great Britain and Northern Ireland

,

Jan B. Derks

⁴Department of Perinatal Medicine, University of Utrecht, Netherlands

,

Caroline J. Shaw

⁶Department of Surgery and Cancer, Imperial College London, United Kingdom of Great Britain and Northern Ireland

,

Tiziana Frusca

⁷Department of Surgical Sciences, Obstetrics and Gynecology Unit, University of Parma, Italy

,

Tullio Ghi

⁷Department of Surgical Sciences, Obstetrics and Gynecology Unit, University of Parma, Italy

,

E. Ferrazzi

⁸Children’s Hospital Buzzi, University of Milan, Italy

,

Christoph C. Lees

⁶Department of Surgery and Cancer, Imperial College London, United Kingdom of Great Britain and Northern Ireland

,

on behalf of the TRUFFLE Group,

TRUFFLE Group authors

(

B. Arabin

⁹Department of Obstetrics and Gynecology, Philipps-University Marburg, Germany

,

C. M. Bilardo

¹⁰Department of Obstetrics, University Medical Centre Groningen, University of Groningen, Netherlands

,

C. Brezinka

¹¹Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Austria

,

A. Diemert

³Department of Obstetrics and Fetal Medicine, University Medical Center, Hamburg-Eppendorf, Germany

,

J. J. Duvekot

¹²Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, Netherlands

,

W. Ganzevoort

²Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands

,

N. Marlow

¹³Department of Academic Neonatology, UCL Institute for Women’s Health, London, UK

,

P. Martinelli

¹⁴Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy

,

E. Ostermayer

¹⁵Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany

,

A. T. Papageorghiou

¹⁶St George’s, University of London, London, UK

,

D. Schlembach

¹⁷Department of Obstetrics, Friedrich Schiller University of Jena, Jena, Germany

,

K. T. M. Schneider

¹⁵Division of Perinatal Medicine, Department of Obstetrics and Gynecology, Technical University, Munich, Germany

,

B. Thilaganathan

¹⁶St George’s, University of London, London, UK

,

J. Thornton

¹⁸Division of Child Health, Obstetrics and Gynecology, School of Medicine, University of Nottingham, UK

,

T. Todros

¹⁹Department of Surgical Sciences, University of Turin Sant’Anna Hospital, Turin, Italy

,

A. Valcamonico

¹Department of Obstetrics and Gynaecology, University of Brescia, Spedali Civili di Brescia, Brescia, Italy

,

A. van Wassenaer-Leemhuis

²⁰Department of Neonatology, Emma Children’s Hospital Academic Medical Centre, Amsterdam, Netherlands

),

TRUFFLE Group collaborating authors

(

A. Aktas

²¹Centre for Mother and Child of the Philips University, Marburg, Germany

,

S. Borgione

²²University of Turin, Sant’Anna Hospital, Turin, Italy

,

R. Chaoui

²³Center of Prenatal Diagnosis and Human Genetics, Berlin, Germany

,

J. M. J. Cornette

¹²Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, Netherlands

,

T. Diehl

²⁴University Medical Center Hamburg-Eppendorf, Hamburg, Germany

,

J. van Eyck

²⁵Department of Perinatology, Isala Clinics, Zwolle, Netherlands

,

I. C. van Haastert

²⁶Department of Neonatology, Division Woman and Baby, UMC Utrecht, Netherlands

,

S. Lobmaier

²⁷Frauenklinik and Poliklinik Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

,

E. Lopriore

²⁸Leiden University Medical Center, Leiden, Netherlands

,

H. Missfelder-Lobos

²⁹Addenbrooke’s Hospital, Cambridge, UK

,

G. Mansi

³⁰Department of Translational Medicine, University of Naples Federico II, Naples, Italy

,

P. Martelli

³¹Department of Child Neuropsychiatry, Spedali Civili Brescia, Italy

,

G. Maso

³²Institute for Maternal and Child Health, IRCCS-Burlo Garofolo, Trieste, Italy

,

U. Maurer-Fellbaum

³³Medical University of Graz, Austria

,

N. Mensing van Charante

²Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands

,

S. Mulderde Tollenaer

³⁴Isala Clincs, Zwolle, Netherlands

,

R. Napolitano

¹⁴Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy

,

M. Oberto

³⁵Department of Obstetrics and Gynecology, University of Turin, Turin, Italy

,

D. Oepkes

³⁶Department of Obstetrics, Leiden University Medical Center, Leiden, Netherlands

,

G. Oggé

³⁵Department of Obstetrics and Gynecology, University of Turin, Turin, Italy

,

J. A. M. van der Post

²Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, Netherlands

,

L. Preston

²⁹Addenbrooke’s Hospital, Cambridge, UK

,

F. Raimondi

³⁰Department of Translational Medicine, University of Naples Federico II, Naples, Italy

,

I. K. M. Reiss

³⁷Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands

,

L. S. Scheepers

³⁸Maastricht University Medical Centre, Maastricht, Netherlands

,

A. Skabar

³²Institute for Maternal and Child Health, IRCCS-Burlo Garofolo, Trieste, Italy

,

M. Spaanderman

³⁹Department of Obstetrics and Gynecology, University Hospital St Radboud, Nijmegen, Netherlands

,

N. Weisglas-Kuperus

³⁷Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands

,

A. Zimmermann

²⁷Frauenklinik and Poliklinik Klinikum rechts der Isar der Technischen Universitat, Munich, Germany

)› Author Affiliations

Abstract

Purpose To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses.

Materials and Methods Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV.

Results We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001).

Conclusion Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.

Zusammenfassung

Ziel Untersuchung des Effekts der antenatalen Gabe von Betamethason auf den fetalen Doppler und die Kurzzeitvariation der fetalen Herzfrequenz (CTG-STV) bei Föten mit früher Wachstumsrestriktion (FGR).

Material und Methoden Post-hoc-Analyse von Daten der TRUFFLE-Studie, einer prospektiven, multizentrischen, randomisierten Managementstudie bei schwerer, früh einsetzender FGR. Wiederholte Doppler- und CTG-STV-Messungen zwischen der letzten Aufnahme innerhalb von 48 Stunden vor der ersten Betamethason-Dosis (Ausgangswert) und über 10 Tage wurden bewertet. Eine mehrstufige Analyse erfolgte, um den longitudinalen Verlauf der umbilikal-zerebralen Ratio (UC-Ratio), des Pulsatilitätsindex des Ductus venosus (DVPIV) und der CTG-STV zu analysieren.

Ergebnisse Wir haben 115 Föten eingeschlossen. Ein signifikanter Anstieg der CTG-STV gegenüber dem Ausgangswert wurde am Tag + 1 (p = 0,019) ermittelt, danach gab es keinen Unterschied. Der DVPIV unterschied sich an keinem der 10 Tage nach erster Betamethason-Dosis signifikant vom Ausgangswert (p = 0,167). Eine mehrstufige Analyse ergab, dass die verstrichene Zeit nach der antenatalen Betamethason-Gabe über 10 Tage hinweg signifikant mit der Abnahme der CTG-STV (p = 0,045) und der Zunahme des DVPIV (p = 0,001) und der UC-Ratio (p < 0,001) assoziiert war.

Schlussfolgerung Obwohl die Steroidverabreichung bei früher FGR eine kleine Auswirkung auf den Anstieg der CTG-STV 1 Tag darauf hatte, waren die Effekte auf die Doppler-Parameter äußerst gering mit Regressionskoeffizienten von geringer Höhe, die nicht auf klinische Signifikanz schließen lassen. Sie stehen höchstwahrscheinlich in Zusammenhang mit der Verschlechterung bei FGR im Laufe der Zeit. Daher bleibt die Beurteilung der arteriellen und venösen Doppler bezüglich des Gesundheitszustandes des Fötus aussagekräftig, nachdem diesem zur Beschleunigung der fetalen Lungenreifung antenatal Steroide verabreicht wurden.

Key words

fetal growth restriction - betamethasone - obstetrics

Full Text

References

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Supplementary Material

Supplementary Material