FDA warns manufacturing fault with membrane test creates fetal death risk
- FDA Wednesday warned patients and providers of potential misuse, overreliance and inaccurate interpretation of tests used to diagnose membrane rupture in pregnant women, noting a risk of adverse events such as fetal harm or death.
- To date, FDA says that it is aware of 13 fetal deaths and other health complications in pregnant women related to the use of ROM tests. If pregnant women are concerned about premature rupture of amniotic membranes, they should promptly speak to a healthcare provider, the agency says.
- The agency specifically called attention to a voluntary recall by Qiagen of approximately 40,500 tests for diagnosing membrane rupture in pregnant women, after reports that some tests lacked the display line needed to interpret the results. Although FDA says it is not aware of adverse events related to the recalled product, the agency classified it as a major, Class I event due to the risk for serious injuries or death.
In most pregnancies, the membrane that surrounds the fetus remains intact until the due date. Once birth is imminent, the membrane is broken down through mechanisms including programed cell death. However, in around 10% of pregnancies the membrane ruptures after 37 weeks of gestation, but before the onset of labor. Around 3% of women experience membrane rupture before the 37th week. This is the leading cause of preterm delivery.
FDA says that it is alerting the public and providers due to the potential risk to pregnant women. In a letter to providers, the agency notes that "health care providers may be over-relying on ROM test results when making critical patient management decisions, despite labeling instructions warning against this practice."
"Our review of the risks associated with improper use of these ROM tests is ongoing, but we want to be transparent with providers and patients about the information that we have indicating an issue, and provide recommendations to minimize the risks," said Courtney Lias, director of the Division of Chemistry and Toxicology Devices in the FDA’s Center for Devices and Radiological Health, in a statement.
Physicians can assess whether the membrane has ruptured through a sterile speculum examination but this is associated with false positives and negatives. The injection of a diagnostic agent into the amniotic sac yields more accurate results but slightly raises the risk of miscarriage.
Qiagen’s immunoassay AmniSure ROM is supposed to offer a better alternative. The test detects placental alpha-microglobulin-1 (PAMG-1), a protein that is found in high concentrations in amniotic fluid and low concentrations in cervicovaginal fluid. The difference in concentrations means the presence of high concentrations of PAMG-1 in the cervicovaginal fluid suggests the membrane has ruptured, releasing protein-rich amniotic fluid.
The immunoassay typically works well, diagnosing membrane rupture with high accuracy. However, a manufacturing defect has affected the performance of some tests. The defect led Qiagen to ship nearly 40,000 tests that may lack a control line.
AmniSure ROM tests should display a control line at all times. A second line becomes visible if a high concentration of PAMG-1 is found in the tested sample. The FDA is concerned that the faulty tests will only display one line when delivering a positive result. This could lead the physician to think the test is negative and not take the necessary actions to care for the patient and their baby, leading to serious adverse events including fetal death.
- FDA Risks Associated with Use of Rupture of Membranes Tests - Letter to Health Care Providers
- FDA FDA alerts healthcare providers, women about risks associated with improper use of rupture of membranes tests
- FDA Qiagen Sciences LLC. Recalls the AmniSure ROM Test Due to Lack of Control Line - Which May Lead to Misinterpretation of Test Results
- NCBI Comparison of rapid immunoassays for rupture of fetal membranes