Three steps identify causes of most stillbirths



SAN FRANCISCO – The cause of stillbirth can be identified in two-thirds of cases by checking the placental histology, conducting an autopsy, and karyotype testing.

That’s a "major, major take-home point" that’s "very different than what I was taught" in medical training, Dr. Yair J. Blumenfeld said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

That finding from an important 2011 study and other new data in the past 5 years suggests that perhaps clinicians should take a staggered approach when ordering tests to search for the etiology of a stillbirth. "Maybe I shouldn’t do a $2,000 workup for thrombophilia and anticardiolipin antibodies if the autopsy showed me that there’s an underlying structural abnormality, or if there’s an abnormal karyotype," he suggested.

Dr. Yair J. Blumenfeld

In general, a growing proportion of stillbirths is being attributed to maternal, fetal, or placental causes, shrinking the proportion relegated to "idiopathic" or unexplained stillbirth. The idea that most stillbirths are idiopathic is "somewhat old thinking" at this point, said Dr. Blumenfeld of Stanford (Calif.) University.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development created the Stillbirth Collaborative Research Network, which developed a new system of determining the causes of stillbirth and tested it in a multicenter, population-based case-control study in five U.S. states during 2006-2008. Potential etiologies for each stillbirth were graded as a possible or probable cause of death based on a complete evaluation including autopsy, placental pathology, medical records, maternal interview, karyotype, and other laboratory tests.

Investigators found a probable cause in 61% of the 512 stillbirths from 500 women and a possible or probable cause in 76%. More than one possible or probable cause was found in 31% of stillbirths, showing some overlap in the causes of stillbirth. The leading causes of antepartum stillbirths were obstetric complications in 29% and placental pathology in 23%, although some of the causes of stillbirth varied significantly by race (JAMA 2011;306:2459-68).

Obstetric complications were less likely to be the cause of stillbirths in white women (in 22%) or Hispanic women (25%), compared with black women (44%) or women of other races (41%). Infection as a cause of stillbirth also was less likely in whites (7%) or Hispanics (8%), compared with blacks (25%) or other races (22%). Hispanics and whites, however, had higher rates of umbilical cord complications as a cause of stillbirth (13% for each), compared with blacks (4%) or other races (5%).

Among the clinically indicated tests for stillbirths, the placental histology identified a cause of stillbirth 52% of the time. An autopsy found a cause in 31% of cases, and karyotype testing identified a cause 9% of the time. Eight other screening tests found a cause for stillbirth in 0.4%-4.8% of cases, depending on the test. These included screens for antibodies, toxicology, or blood glucose; tests for syphilis, parvovirus, lupus anticoagulant, or anticardiolipin antibody; or detection of fetal blood in fetal-maternal hemorrhage.

"I’m not saying we shouldn’t do these things, but I think in today’s health care climate, especially with health care economics, you should start to think about maybe a staggered approach" in order to control costs, Dr. Blumenfeld said.

Controversy surrounds several topics in the search for stillbirth etiologies: whether chromosomal microarrays are better than karyotype testing; whether or not to order screening for thrombophilias and antiphospholipid antibodies; and what to do if the parents reject an autopsy.

In a study of 532 stillbirths, chromosomal microarray testing yielded results more often than did karyotyping – in 87% of cases vs. 71% – and detected aneuploidy or copy number variants more often, in 8.8% of cases vs. 6.5% (New Engl. J. Med. 2012;367:2185-93). Whether that difference is worth a price tag of approximately $2,000 for microarray testing remains to be seen, but "we’re going to see a lot more studies" of stillbirths using this and other new technologies, Dr. Blumenfeld said.

Practice bulletins from the American College of Obstetricians and Gynecologists are "all over the map" when it comes to deciding whether or not to test for thrombophilias and antiphospholipid antibodies when there’s a stillbirth," he said. "It’s still very, very controversial." It’s probably wise to use the results of autopsy, karyotyping, and placental histology to help decide whether to pursue these other tests, and to talk with patients about their family history of thrombophilia, what the placenta looked like, and other factors that could guide decision-making, he added.

How health care providers counseled parents affected parents’ decision to accept or decline an autopsy of their stillborn infant in 22% of cases, according to one study of 460 parents, 354 obstetricians, 21 perinatal pathologists, and 2,256 midwives (BJOG 2012;119:987-97). Altogether, 62% of parents agreed to an autopsy.


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