Selective Fetal Growth Restriction in Monochorionic Twins - an International Investigation (CONTRAST)

Optimal diagnostic management and underlying pathophysiological mechanisms of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies have not been fully clarified.

The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the predictive value is limited. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double fetal demise. Outcome prediction is furthermore important in the selection of cases that will be offered selective reduction (to provide the larger twin with better prospects), as well as determining monitor frequency and possible hospital admission. As outcome prediction is clinically challenging, patient counselling is too, and parents often encounter a great deal of uncertainty during the pregnancy.

Furthermore, little is known about the brain development of sFGR children (both during pregnancy and after birth). Moreover, the psychological impact of an sFGR pregnancy of the future parent)s) has not been studied before. The impact of these factors should be taken into account during patient counseling, which is currently not the case.

By our knowledge, this is the first international, multicenter, prospective cohort study on that will address the abovementioned questions and knowledge gaps in MCDA pregnancies complicated by selective fetal growth restriction.

Study Overview

• Status: Recruiting
• Conditions: Fetal Growth Retardation; Twin; Pregnancy, Affecting Fetus or Newborn; Twin Diseases; Twin Monochorionic Diamniotic Placenta
• Intervention / Treatment: Diagnostic test: Ultrasound

Detailed Description

Selective fetal growth restriction (sFGR) in monochorionic twins may negatively impact the pregnancy. There is a substantial risk of fetal deterioration resulting in (iatrogenic) preterm birth or even intrauterine demise of one, or both fetuses. There are important unresolved challenges on a diagnostic level and underlying pathophysiological mechanisms of sFGR have not been fully clarified.

The current diagnostic classification system based on three different umbilical artery flow patterns has no increasing scale of severity and the observed flow patterns may be volatile in nature. This hinders optimal diagnostic management and complicates outcome prediction as the survival outcome differs per umbilical artery flow type. Consequently, parents encounter a great deal of uncertainty during the pregnancy. Since there is no treatment available for sFGR, predicting fetal deterioration is key in preventing single or double demise.

By testing several predictors, the investigators are aiming to improve outcome prediction at the time of sFGR diagnosis. The investigators furthermore hypothesize that additional ultrasound parameters could be of benefit in making the current classification system more accurate and less variable. Extensive histological placental examinations will shine a light on microscopic abnormalities which can increase our knowledge of the pathophysiology. Examining neurodevelopment of sFGR twins at two years of age will additionally be of great value for our understanding of the impact of sFGR and contribute to adequate patient counselling. Our study will evaluate the impact of a sFGR pregnancy on parental mental health and parent-to-infant(s) attachment, which has not been carried out this extensively before.

• Study Type: Observational
• Enrollment (Estimated): 274

Contacts and Locations

• Study Contact: Name: Anne Noll, MD; Phone Number: +32 16 34 47 50; Email: a.t.r.noll@lumc.nl

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitaire Ziekenhuizen Leuven
    • Contact: Liesbeth Lewi, MD phD
• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 1X5
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Shiri Shinar, MD PhD
• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Recruiting
      • Leiden University Medical Center
      • Contact: Joanne Verweij, MD PhD
• Spain
  • Barcelona, Spain, 08028
    • Recruiting
    • BCNatal
    • Contact: Mar Bennasar, MD PhD
• Sweden
  • Stockholm, Sweden, 17164 Solna
    • Not yet recruiting
    • Karolinska University Hospital
    • Contact: Lotta Herling, MD PhD
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Ali Javinani, MD, PhD; Email: contraststudy@childrens.harvard.edu
      • Contact: Alireza Shamshirsaz, Professor, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

MCDA pregnancies complicated by sFGR pregnancies that meet the inclusion criteria.

Description

Inclusion Criteria:

• MCDA twin pregnancy
• Diagnosis of sFGR before 28+0 weeks of GA (independent of Doppler flows)
• Pregnant woman ≥ 18 years and able to consent
• Partner (who has (future) parental responsibility - if applicable) ≥ 18 years and able to consent
• Written informed consent of both parents (if applicable) for participation in the longitudinal follow-up until 2 years after birth)

Exclusion Criteria:

• The presence of lethal anomalies (one or both fetuses)
• Multiple pregnancy higher order than twins;
• TTTS/TAPS present at moment of sFGR diagnosis.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
sFGR cohort; Monochorionic diamniotic twin pregnancies complicated by sFGR (diagnosed before 28 weeks of gestational age)	Diagnostic test: Ultrasound; Additional ultrasound measurements during pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome	The composite outcome consists of fetal single or double demise, including selective fetal reduction and/or an iatrogenic elective birth < 32 weeks of gestational age because of fetal distress).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasound parameters	Explanatory analysis of ultrasound parameters over course of sFGR pregnancy	2 years
Prenatal and postnatal attachment		2 years
Post-traumatic stress		2 years
PARCA-R evaluation		2 years

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Karolinska University Hospital; Universitaire Ziekenhuizen KU Leuven; Boston Children's Hospital; MOUNT SINAI HOSPITAL; BCNatal Fetal Medicine Research Center

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: sFGR; sIUGR; selective fetal growth restriction
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Growth Retardation
• Other Study ID Numbers: CONTR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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