Amniotic Fluid Tandem Mass Spectrometry for Pregnancies Complicated by NIH and Severe Symmetrical IUGR (TandemMS)

Amniotic Fluid Tandem Mass Spectrometry for Pregnancies Complicated by Nonimmune Hydrops and Severe Symmetrical Intrauterine Growth Restriction-A Multicenter Prospective Pilot Cohort Study

The objective of this pilot study is to prospectively evaluate amniotic fluid of pregnancies complicated by non-immune hydrops and severe symmetrical intrauterine growth restriction by tandem mass spectrometry for inborn errors of metabolism.

Study Overview

• Status: Terminated
• Conditions: Fetal Growth Retardation; Hydrops Fetalis
• Intervention / Treatment: Procedure: Tandem MS test for inborn errors of metabolism

Detailed Description

Nonimmune hydrops (NIH) and severe symmetrical intrauterine growth restriction (IUGR) represent two obstetrical circumstances that occur with relative frequency yet often escape adequate etiology assessment and diagnosis prior to and after birth. Both of these conditions have high perinatal and neonatal mortality rates. While antepartum ultrasound and amniotic fluid evaluations of fetal karyotype and viral DNA studies diagnose some etiologies for NIH and severe symmetrical IUGR, large percentages of NIH (30-40%) and IUGR (20-30%) cases are attributed to idiopathic causes. Because of this uncertainty in diagnosis, many cases are subjected to prolonged antepartum hospitalization with intensive fetal monitoring and urgent delivery by Cesarean section for non-reassuring fetal status, only to succumb to a neonatal demise in the nursery. A small percentage (1-2%) of these cases are found to be due to inborn errors of metabolism by neonatal and/or postmortem evaluation; however, when combined together, greater than 50% of NIH and IUGR cases have no identifiable etiology. Therefore, any new test that may make a diagnosis for NIH or severe symmetrical IUGR prior to delivery would be extremely important to the management of both the mother and the infant. Tandem mass spectrometry for inborn errors of metabolism may represent a new tool for assessing, identifying, and treating currently unexplained cases of NIH and severe symmetrical IUGR.

This is a prospective pilot cohort study of all pregnancies complicated by NIH and severe symmetrical IUGR within the Pediatrix-Obstetrix network. This network encompasses several perinatal sites throughout the United States with corresponding neonatal intensive care units utilizing a computerized patient database (RDS). The objective of this study is to prospectively evaluate amniotic fluid of pregnancies complicated by NIH and severe symmetrical IUGR by a method called tandem mass spectrometry for inborn errors of metabolism.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Good Sammaritan Hospital
    • Phoenix, Arizona, United States, 85202
      • Banner Desert Samaritan Hospital
  • California
    • Laguna Hills, California, United States, 92653
      • Saddleback Memorial Medical Center
    • Long Beach, California, United States, 90801-1428
      • Long Beach Memorial Medical Center
    • San Jose, California, United States, 95124
      • Good Samaritan Hospital
  • Colorado
    • Denver, Colorado, United States, 80110
      • Swedish Medical Center
    • Denver, Colorado, United States, 80218
      • Presbyterian/St Luke's Hospital
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Harris Methodist Fort Worth Hospital
  • Washington
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnancies complicated by NIH or SSIUGR fetuses as compared to a control group of pregnancies with normally appearing fetuses requiring a diagnostic amniocentesis as part of her care.

Description

NIH Inclusion Criteria:

• Singleton gestation
• 18 years of age or older
• Excess extracellular fluid in at least two fetal sites as noted by ultrasound: abdomen (ascites), the chest (pleural and pericardial effusions), the skin (edema > 5mm), the amniotic cavity (polyhydramnios), and the placenta (thickening > 6cm)
• NIH diagnosis > 15w0d gestation
• Diagnostic amniocentesis performed at > 15w0d gestation

NIH Exclusion Criteria:

• Immune-mediated hydrops fetalis as diagnosed by maternal red cell antigens and fetal anemia suspected by middle cerebral artery doppler ultrasound and/or confirmed by percutaneous umbilical blood sampling
• Structural anomaly identified by ultrasound
• Chromosomal aneuploidy
• Multiple gestations

IUGR Inclusion Criteria:

• Singleton gestation
• 18 years of age or older
• Severe symmetrical IUGR defined as a > 3 week lag of all fetal ultrasound measurements (biparietal diameter, head circumference, abdominal circumference, and femur length)
• IUGR diagnosis between 24-32 weeks gestation
• Diagnostic amniocentesis performed prior to 32 weeks gestation

IUGR Exclusion Criteria:

• Asymmetrical IUGR
• Structural anomaly identified by ultrasound
• Chromosomal aneuploidy
• Multiple gestations

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NIH/SSIUGR fetuses; Group 1 includes pregnancies complicated by a fetus with either Non-Immune Hydrops or Severe Symmetrical IUGR.	Procedure: Tandem MS test for inborn errors of metabolism; Tandem MS spectrometry test will be done on all maternal blood, amniotic fluid and newborn blood samples for both groups.; Other Names: Tandem MS
Control-Normal fetus; Group 2 includes all normally appearing fetuses on U/S who will be having a diagnostic amniocentesis as part of their routine care.	Procedure: Tandem MS test for inborn errors of metabolism; Tandem MS spectrometry test will be done on all maternal blood, amniotic fluid and newborn blood samples for both groups.; Other Names: Tandem MS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Will assess whether amniotic fluid tandem mass spectrometry results are valid when compared to neonatal blood samples for normal pregnancies and those pregnancies complicated by NIH and severe symmetrical IUGR.	Will assess whether amniotic fluid tandem mass spectrometry results are valid when compared to neonatal blood samples for normal pregnancies and those pregnancies complicated by NIH and severe symmetrical IUGR.	comparrison down with in 2 days of life.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Neonatal Complications	Will include neonatal complications in pregnancies complicated by NIH and severe symmetrical IUGR.	during the neonatal period

Collaborators and Investigators

• Sponsor: Obstetrix Medical Group
• Investigators: Principal Investigator: Karrie Francois, MD, Pediatrix-Obstetrix Medical Group, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 31, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Estimate): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 17, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: NIH; Severe Symmetrical IUGR; Tandem Mass Spectrometry; Nonimmune Hydrops; Severe Symmetrical Intrauterine Growth Restriction
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Fetal Diseases; Pregnancy Complications; Hemoglobinopathies; Growth Disorders; Erythroblastosis, Fetal; alpha-Thalassemia; Thalassemia; Edema; Fetal Growth Retardation; Hydrops Fetalis
• Other Study ID Numbers: OBX 0005.3; Tandem MS - 0005.3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No