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

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.

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.

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