A systematic pathologic examination of the fetus and placenta is the single most useful test in identifying the cause of IUFD (1). Such an examination can identify such causes as placental abruption, cord accidents, and previously undiagnosed fetal structural anomalies (such as anencephaly) (1-3). If the family declines a request for fetopsy, a careful history and gross examination of the fetus alone may be able to identify the cause in many instances (1). It should be remembered that, even after intensive investigation, around 25-50% of fetal demises will have no known cause (1-3).

What test should be performed immediately as it cannot be done a few weeks later?

A Kleihauer-Betke (KB) test should be sent as soon as possible. This is an acid elution test performed on maternal venous whole blood that is designed to identify fetal cells within the maternal circulation. The KB test will also estimate the quantity of the fetal-maternal hemorrhage, although it is not particularly sensitive at low volumes (<5-mL). This test is commonly used in Rh-negative parturients to estimate the amount of RhoGAM that should be given to prevent Rh isoimmunization. In the setting of an unexplained IUFD, this test should be sent as soon as possible, since fetal erythrocytes are rapidly removed from the maternal circulation. A strongly positive KB test (for example, >30-mL) in the setting of an unexplained IUFD may suggest that the likely cause of the demise was feto-maternal hemorrhage. The KB test is positive in around 5-13% of cases of unexplained IUFD (1,4).

Is there any utility in doing a fetal karyotype?

Because 5-10% of all stillborn infants will have chromosomal abnormalities (5), a karyotype should be sent whenever fetal anatomic malformations are noted. If the index of suspicion is high (for example, if multiple structural anomalies were identified on antepartum ultrasound), consideration should be given to performing amniocentesis in the setting of IUFD to collect viable amniocytes for analysis (6). Sampling of fetal tissues following delivery may have a higher rate of failed karyotype analysis. If the fetus is noted to be macerated, tissue from the umbilical cord or chorionic membranes should be submitted for chromosomal analysis (1). Whether it is necessary to check the karyotype of structurally normal fetuses, however, is not clear.

What other test might be useful, and when should they be performed?

Routine testing for the presence of congenital infections (such as cytomegalovirus, herpes simplex virus, toxoplasmosis, and rubella) either by culture or serologic testing are rarely useful (1,7). Moreover, examination of the placenta will likely identify the vast majority of infections (for example, microabscesses in the setting of listeria or inclusion bodies in toxoplasmosis). If desired, serologic testing should be performed as close to the event as possible in order to better define the likely timing of the infection.

Other tests that are commonly sent include:

Test	Is test reliable in pregnancy?
Type and scre	Yes (screen all patients for isoimmunization)
VDRL or RPR	Yes (screen all patients for syphilis)
Serum glucose	No (screen for diabetes after puerperium)
Urine toxicology screen	Yes
Factor V Leiden deficiency	Yes (genetic test)
Prothrombin gene defect	Yes (genetic test)
MTHFR gene mutation	Yes (genetic test)
Hyperhomocysteinemia	Unknown (test for circulating levels)
Protein C deficiency	No (levels may increase in pregnancy)
Protein S deficiency	No (levels decrease in pregnancy)
Antithrombin III deficiency	No (levels may increase in pregnancy)
Lupus anticoagulant	Yes (ELISA test for circulating antibodies, but more false-positive tests in pregnancy)
Anticardiolipin antibodies	Yes (ELISA test, but more false-positive tests in pregnancy)
Antinuclear antibodies	Yes (ELISA test, but more false-positive tests in pregnancy)