In Utero Repair of Myelomeningocele: Atosiban Versus Terbutaline

Assessment of Maternal Blood Gas Changes When Using Atosiban and Terbutaline as Tocolytic Agents, During in Utero Repair of Myelomeningocele

Myelomeningocele is a malformation with high incidence, and it consists in a neural tube defect. Fetal intrauterine surgery is an alternative for correction, and it improves the prognosis of the fetus, but has an increased risk of maternal complications and premature labor, as it can occur due to uterine stimulation. It is therefore essential that tocolysis is performed before, during and after surgery, and the most commonly used tocolytics are terbutaline and atosiban. Terbutaline has no specificity and may have several adverse effects such as maternal acidosis.

Study Overview

• Status: Completed
• Conditions: Myelomeningocele; Terbutaline Adverse Reaction; Pregnancy; Malformation Central Nervous System
• Intervention / Treatment: Drug: Atosiban; Drug: Terbutaline

Detailed Description

The objective of the study was to evaluate maternal blood gas alterations among cases that used atosiban tocolytic agent and cases with terbutaline in in utero repair of myelomeningocele. It consists of a retrospective cohort study. It included 25 patients, who were divided into two groups, depending on which agent they received as main tocolytic agent during the intrauterine fetal myelomeningocele repair: terbutalineor atosiban. The primary outcome was maternal arterial pH at the end of surgery.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Faculdade de Medicina da Universidade de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Patients who underwent intrauterine myelomeningocele surgical repair in a tertiary obstetrical center (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), from November of 2017 to January of 2020.

Description

Inclusion Criteria:

• Pregnant women over 18 years
• Single fetus pregnancy
• Fetus with myelomeningocele
• Gestational age from 19 to 26
• Fetus with normal karyotype

Exclusion Criteria:

• Multiple pregnancy
• Fetal abnormality not related to myelomeningocele
• Kyphosis greater than or equal to 30 degrees
• Placenta previa
• Maternal disease that increases the risk of pregnancy (insulin-dependent DM, hypertension poorly controlled)
• History of incompetent cervix
• Carrier of HIV, hepatitis B or hepatitis C
• Maternal-fetal isoimmunization
• Uterine Alteration
• Obesity (IMC greater than 30)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Atosiban; Intravenous Atosiban as main tocolytic agent	Drug: Atosiban; Atosiban intravenous. Dose: attack of 6.75 mg, and maintenance of 300 mcg / min for 3 hours, and 100 mcg / min for 21 hours.
Terbutaline; Intravenous Terbutaline as main tocolytic agent	Drug: Terbutaline; Terbutaline intravenous. Dose: 2.5 mg in 500 mL saline, infusion rate of 30 mL / hr (150 mcg / h) during the surgery and for 24 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal arterial blood pH at the start of surgery	Arterial blood pH	Right after intubation
Maternal arterial blood pH at the end of surgery	Arterial blood pH	Before extubation
Maternal arterial blood pH at 120 minutes after surgery	Arterial blood pH	Two hours after the end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term fetal repercussions	Fetal heart rate in the immediate postoperative period	In the end of the surgery, before extubation
Long-term fetal repercussions	Gestational age at birth	At the birth

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Elaine I Moura, MD, Hospital das Clínicas; Principal Investigator: Hermann S Fernandes, PhD, Hospital das Clínicas

Publications and helpful links

General Publications

• Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.
• Ferschl M, Ball R, Lee H, Rollins MD. Anesthesia for in utero repair of myelomeningocele. Anesthesiology. 2013 May;118(5):1211-23. doi: 10.1097/ALN.0b013e31828ea597.
• Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, Meyer R, Canfield MA, Mulinare J; National Birth Defects Prevention Network. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol. 2008 Jul;82(7):527-32. doi: 10.1002/bdra.20468.
• Fichter MA, Dornseifer U, Henke J, Schneider KT, Kovacs L, Biemer E, Bruner J, Adzick NS, Harrison MR, Papadopulos NA. Fetal spina bifida repair--current trends and prospects of intrauterine neurosurgery. Fetal Diagn Ther. 2008;23(4):271-86. doi: 10.1159/000123614. Epub 2008 Apr 14.
• Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001 Oct;95(4):828-35. doi: 10.1097/00000542-200110000-00008.
• Cauldwell CB. Anesthesia for fetal surgery. Anesthesiol Clin North Am. 2002 Mar;20(1):211-26. doi: 10.1016/s0889-8537(03)00062-2.
• Devoto JC, Alcalde JL, Otayza F, Sepulveda W. Anesthesia for myelomeningocele surgery in fetus. Childs Nerv Syst. 2017 Jul;33(7):1169-1175. doi: 10.1007/s00381-017-3437-7. Epub 2017 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: March 1, 2020
• First Submitted That Met QC Criteria: July 10, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Nervous System Malformations; Neural Tube Defects; Spinal Dysraphism; Meningomyelocele; Spina Bifida Cystica; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Hormone Antagonists; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Atosiban; Terbutaline
• Other Study ID Numbers: 00607219.4.0030.0099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD sharing plan includes informations about the demographic sample, the results of the study and the statistical analysis
• IPD Sharing Time Frame: From October/2017 until January/2021
• IPD Sharing Access Criteria: Contact through email
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No