Is it possible for a fetus to develop a fetal intrauterine cerebral infarct (diagnosed after birth by MRI) from an antiphospholipid syndrome (APS) positive mother?

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Is it possible for a fetus to develop a fetal intrauterine cerebral infarct (diagnosed after birth by MRI) from an antiphospholipid syndrome (APS) positive mother? She delivered twins at 38 weeks. Both non-identical twins survived, one was normal.


While the classic obstetrical complications of antiphospholipid syndrome (APS) are fetal distress or fetal loss, fetal and neonatal thromboses have certainly been described in offspring of antiphospholipid (aPL) -positive mothers. The term "neonatal antiphospholipid syndrome" has even been suggested, but unlike the neonatal lupus syndrome associated with anti-Ro/SS-A and anti-La/SS-B antibodies, only rare case reports support this as a potential manifestation of aPL.

Maternal antiphospholipid antibodies (like many autoantibodies) do cross the human placenta, and documented elevated levels in newborns disappear by about 6 months. Cohort studies of aPL pregnancy outcomes identify prematurity – with its attendant complications – as a significant adverse outcome, but not fetal or neonatal thrombosis. One explanation for the very low incidence of thrombosis may be the differential placental transfer of human antibody. Only IgG, and not IgM, antibodies pass through the human placenta; however, not all IgG subclasses are transferred to an equal degree: transfer of IgG1 and IgG3 is markedly greater than that of IgG2 and IgG4. Recent work has shown IgG2, however, to be the anticardiolipin IgG subclass most closely associated with thrombosis; hence, it may be that the most efficiently transferred antibodies have a lower potential for pathogenicity.

A number of case reports describe convincing examples of fetal and neonatal thrombosis. At least seven cases of neonatal cerebral ischemia have been reported (most in the middle cerebral artery distribution) in offspring of aPL-positive mothers with demonstrated aPL antibody in the infant. Other reports support additional types of thrombotic complications, including aortic, renal vein, and other thromboses, and even a catastrophic APS syndrome in one infant. Fetal thrombosis, as in your patient’s case, has also been reported in with hydrops fetalis and fetal vein thrombosis.

Why was one (nonidentical) twin affected in your patient’s case, and not the other? Current theory of the mechanism of aPL-related complications suggests that a "second hit" is required – something that may have been present in one twin but not the other, for example, endothelial activation, or a relatively lower level of antithrombin III (which increases only gradually during fetal development). Instrumentation with catheters may trigger thrombosis in neonates. Genetic prothrombotic risk factors - such as factor V Leiden or the prothrombin G20210A mutation - may also differ between siblings, and presence of these has been shown to increase risk of thrombosis in patients with aPL. Since the antibodies are transient in the newborn, unless the affected infant has other prothrombotic risk factors (or persistent aPL of his or her own), there should be no need for long-term anticoagulation.



Botet F, Romera G, Montagut P, et al. Neonatal outcome in women treated for the antiphospholipid syndrome in pregnancy. J Perinat Med 1997;25:192-196.

Silver RK, MacGregor SN, Pasternak JF, Neely SE. Fetal stroke associated with elevated maternal anticardiolipin antibodies. Obstet Gynecol 1992;80:497-499.

Navarro F, Dona-Naranjo MA, Villanueva I. Neonatal antiphospholipid syndrome. J Rheumatol 1997;24:1240-1241.


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