Half of Stillbirths Unexplained; Don't Overlook Infection as Cause


ASHEVILLE, N.C. — When looking for causes of stillbirth, obstetricians and pediatricians should not overlook infection, Dr. Sean Blackwell said at the Southern Obstetric and Gynecologic Seminar.

Though the fetal death rate has declined, about half of stillbirths are due to unexplained causes, said Dr. Blackwell of the maternal fetal medicine division at William Beaumont Hospital in Royal Oak, Mich.

A recent paper (Sem. Perinatol. 2006;30:20–3) hypothesized that at least 10% of stillbirths result from infection, a rate equal to the number of deaths caused by fetal anomalies but slightly less than those caused by fetal growth restriction (14%), abruption (14%), or cord- or placenta-related problems (18%). The same study estimated that 27% of stillbirths have unexplained causes.

The number of unexplained stillbirths increases with rising gestational age, said Dr. Blackwell, adding that some of these cases may be undiagnosed or undetected infection.

A variety of pathogens have been associated with stillbirth, including spirochetes, protozoans, viruses, and bacteria, he said. There are three potential ways a fetus can acquire an infection: through systemic maternal illness; through the cervicovaginal compartment; or via a transplacental route. Maternal illness may result in a proinflammatory response that redistributes blood flow, leading to uteroplacental insufficiency.

An ascending infection will infect fetal and placental tissue, leading to sepsis. Group B streptococci, Escherichia coli, Ureaplasma, and Candida are known to use the ascending route, said Dr. Blackwell.

Similarly, a pathogen that crosses the placental barrier will infect fetal and placental tissue, leading to sepsis and anomalies. Malaria, syphilis, coxsackievirus, cytomegalovirus, and parvovirus are known to cross the placenta.

Dr. Blackwell said that several papers have shown that parvovirus may lead to fetal death by previously unknown mechanisms. In testing tissue from stillbirths with unexplained causes, Dr. Blackwell and colleagues found that though 43 of the 44 had negative cultures, there were changes in the tissue consistent with exposure to an infectious agent (J. Matern. Fetal Neonatal Med. 2003;14:151–7 and 241–6).

Recent findings show that genetics may also play a role in susceptibility to stillbirth. Some women have a polymorphism that appears to cause hyperresponsiveness to infections like bacterial vaginosis, resulting in a proinflammatory cascade that could harm the fetus. There is growing evidence also that fetal response to infection may be partly governed by phenotypes. Several papers have postulated that there may be a normal response in which the fetal immune response results in the triggering of labor, which helps the fetus escape a hostile environment, Dr. Blackwell said. He urged clinicians to conduct full work-ups on stillbirths, including taking cultures of the placenta and blood and organs of the fetus in order to get some answers.

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